Cyclohexyl-1, 4-diamine compounds

ABSTRACT

Novel cyclohexyl-1,4-diamine compounds corresponding to formula I, 
                         
processes for the production thereof, pharmaceutical compositions containing these compounds, methods of producing pharmaceutical compositions including these compounds and related methods of treating or inhibiting certain diseases or conditions.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of International patent application Serial No. PCT/EP2005/004913 filed May 6, 2005 which claims benefit to German patent application Serial No. 10 2004 023 522.8 filed May 10, 2004, the entire disclosures of which are hereby incorporated in their entirety.

FIELD OF THE INVENTION

The present invention relates to cyclohexyl-1,4-diamine compounds, processes for the production thereof, pharmaceutical compositions containing these compounds, methods of producing pharmaceutical compositions including these compounds and related methods of treating or inhibiting certain diseases or conditions.

BACKGROUND OF THE INVENTION

The treatment of chronic and non-chronic pain conditions has great importance in medicine. There is a worldwide need for effective methods of treating pain. The urgent need for action for patient-oriented and purposeful treatment of chronic and non-chronic pain conditions, this being taken to mean the successful and satisfactory treatment of pain for the patient, is documented in the large number of scientific papers which have recently appeared in the field of applied analgesics and fundamental research work on nociception.

Conventional μ-opioids such as morphine are very effective in the treatment of strong to very strong pain and are of great importance for the treatment of pain. However, it may be advantageous if, in addition to the μ-opioid receptor, further opioid receptors, in particular the ORL1 receptor, are affected, since pure μ-opioids also have undesirable side effects, such as obstipation and respiratory depression, and may also lead to addiction. The opioid receptors δ, κ and ORL1 are also involved in the state of pain (Opioids: Introduction, pp. 127-150, Further Opioid Receptors, 455-476 in: Analgesics—From Chemistry and Pharmacology to Clinical Application, Wiley VCH, 2002).

It is also known that influencing of serotonin and/or noradrenalin re-uptake can be beneficial to the effects and side effects of opioids (Example: Tramadol, see Opioids with Clinical Relevance: Tramadol, 228-230 in: Analgesics—From Chemistry and Pharmacology to Clinical Application, Wiley VCH, 2002).

The ORL1 receptor is also involved in the regulation of further physiological and pathophysiological processes. These include inter alia learning and memory formation (Manabe et al, Nature, 394, 1997, pp. 577-581), Hörvermögen [Hearing capacity] (Nishi et al, EMBO J., 16, 1997, pp. 1858-1864) and numerous further processes. In a synopsis by Calo et al (Br. J. Pharmacol., 129, 2000, 1261-1283) there is an overview of the indications or biological procedures, in which the ORL1 receptor plays a part or could highly probably play a part. Mentioned inter alia are: analgesics, stimulation and regulation of nutrient absorption, effect on μ-agonists such as morphine, treatment of withdrawal symptoms, reduction of the addiction potential of opioids, anxiolysis, modulation of motor activity, memory disorders, epilepsy; modulation of neurotransmitter release, in particular of glutamate, serotonin and dopamine, and therefore neurodegenerative diseases; influencing the cardiovascular system, triggering an erection, diuresis, anti-natriuresis, electrolyte balance, arterial blood pressure, water-retention disorders, intestinal motility (diarrhoea), relaxation of the respiratory tract, micturation reflex (urinary incontinence). The use of agonists and antagonists such as anoretics, analgesics (also when administered with opioids) or nootropics will also be discussed.

Structurally related compounds which have an affinity with the ORL1 receptor are known from the prior art (WO 02090317). The effect on noradrenalin and serotonin re-uptake has not previously been described for this structural class.

SUMMARY OF THE INVENTION

An object of the present invention was to provide pharmaceutical compositions which act on the opioid receptor system and are thus suitable for pharmaceutical compositions, in particular for the treatment of the various diseases associated with this system according to the prior art and for use in the indications mentioned therein. The compounds are also intended to influence noradrenalin and serotonin re-uptake

The invention therefore relates to substituted cyclohexyl-1,4-diamine derivatives of general formula I,

wherein

n represents 1, 2, 3, 4 or 5

R¹ and R² independently of one another represent H; respectively saturated or unsaturated, branched or unbranched, singly or multiply substituted or unsubstituted C₁₋₅ alkyl; respectively singly or multiply substituted or unsubstituted C₃₋₈-cycloalkyl; or respectively singly or multiply substituted or unsubstituted aryl, C₃₋₈ cycloalkyl or heteroaryl bound by C₁₋₃ alkyl;

or the radicals R1 and R2 together represent CH2CH2OCH2CH2, CH2CH2NR10CH2CH2 or (CH2)3-6,

wherein R¹⁰ represents H; respectively saturated or unsaturated, branched or unbranched, singly or multiply substituted or unsubstituted C₁₋₅ alkyl respectively singly or multiply substituted or unsubstituted C₃₋₈ cycloalkyl; respectively singly or multiply substituted or unsubstituted aryl or heteroaryl; or respectively singly or multiply substituted or unsubstituted aryl, C₃₋₈ cycloalkyl or heteroaryl bound by C₁₋₃ alkyl; respectively substituted or unsubstituted C(O)phenyl, C(O)heteroaryl, C(O)C₁₋₅ alkyl;

R³ represents respectively saturated or unsaturated, branched or unbranched, singly or multiply substituted or unsubstituted C₁₋₅ alkyl; respectively singly or multiply substituted or unsubstituted C₃₋₈ cycloalkyl; respectively unsubstituted or singly or multiply substituted aryl or heteroaryl; respectively unsubstituted or singly or multiply substituted aryl, heteroaryl or C₃₋₈ cycloalkyl bound by a C₁₋₃ alkyl group;

R⁴ represents —(CR⁶R⁷)_(p)R ⁸,

wherein p represents 0, 1, 2, 3 or 4

R⁶ represents H or respectively saturated or unsaturated, branched or unbranched, unsubstituted or singly or multiply substituted C₁₋₅ alkyl,

R⁷ represents H, respectively saturated or unsaturated, branched or unbranched, unsubstituted or singly or multiply substituted C₁₋₅ alkyl or COOR⁹,

or R⁶ and R⁷ form a ring (CH₂)_(k)CHR⁸(CH₂)m, where k=1, 2, 3 and m=1, 2

R⁸ represents respectively saturated or unsaturated, branched or unbranched, unsubstituted or singly or multiply substituted C₁₋₆ alkyl, respectively unsubstituted or singly or multiply substituted C₃₋₈ cycloalkyl, aryl or heteroaryl,

R⁹ represents H or C₁₋₅ alkyl

R⁵ represents H or —(CH₂)_(l)R⁸,

wherein l represents 1, 2 or 3,

or together with R⁴ represents CH₂CHR¹⁴OCHR¹⁴CH₂, CH₂CH₂SCH₂CH₂

CH₂CH₂NR¹¹CH₂CH₂, (CR¹²R¹³)₃₋₆ or

wherein R¹¹ represents H; respectively saturated or unsaturated, branched or unbranched, singly or multiply substituted or unsubstituted C₁₋₅ alkyl; respectively saturated or unsaturated, singly or multiply substituted or unsubstituted C₃₋₈ cycloalkyl; respectively singly or multiply substituted or unsubstituted aryl or heteroaryl; or respectively singly or multiply substituted or unsubstituted aryl, C3-8 cycloalkyl or heteroaryl bound by C₁₋₃ alkyl;

R¹² represents H; respectively saturated or unsaturated, branched or unbranched, singly or multiply substituted or unsubstituted C₁₋₅ alkyl; OH; unsubstituted or singly or multiply substituted C(O)phenyl; respectively singly or multiply substituted or unsubstituted C₃₋₈ cycloalkyl; respectively singly or multiply substituted or unsubstituted aryl or heteroaryl; or respectively singly or multiply substituted or unsubstituted aryl, C₃₋₈ cycloalkyl or heteroaryl bound by C₁₋₃ alkyl;

and R¹³ represents H or OH or together with R¹² via the same C atom (spiro compound) or an adjacent C atom forms a five-membered or six-membered ring which may contain heteroatoms, be saturated or unsaturated, substituted or unsubstituted and/or be part of a polycyclic system;

R¹⁴ represents H or respectively saturated or unsaturated, branched or unbranched, singly or multiply substituted or unsubstituted C₁₋₃ alkyl;

in the form of the racemate; the enantiomers, diastereomers, mixtures of the enantiomers or diastereomers or an individual enantiomer or diastereomer; the bases and/or salts of physiologically acceptable acids or cations.

The compounds according to the invention exhibit good binding to the μ receptor and the ORL1 receptor, but also to other opioid receptors. Surprisingly it has been found that the compounds are also good inhibitors of noradrenalin and serotonin re-uptake. They are therefore also suitable for treating depression and/or bulimia and/or anorexia and/or catalepsy and/or anxiolysis and/or increasing alertness and/or libido.

The terms “C₁₋₆ alkyl”, “C₁₋₅ alkyl” and “C₁₋₃ alkyl” comprise, in the context of this invention, acyclic saturated or unsaturated hydrocarbon radicals, which may be branched or straight-chained and unsubstituted or singly or multiply substituted, with 1, 2, 3, 4, 5 or 6 C atoms or 1, 2, 3, 4 or 5 C atoms or 1, 2 or 3 C atoms, i.e. C₁₋₆ alkanyls, C₂₋₆ alkenyls and C₂₋₆ alkynyls or C₁₋₅ alkanyls, C₂₋₅ alkenyls and C₂₋₅ alkynyls or C₁₋₃ alkanyls, C₂₋₃ alkenyls and C₂₋₃ alkynyl. Alkenyls have at least one C—C double bond and alkynyls at least one C—C treble bond. Alkyl is advantageously selected from the group comprising methyl, ethyl, n-propyl, 2-propyl, n-butyl, iso-butyl, sec.-butyl, tert.-butyl, n-pentyl, iso-pentyl, neo-pentyl, n-hexyl, 2-hexyl, 2,3-dimethylbutyl; ethylenyl (vinyl), ethynyl, propenyl (—CH₂CH═CH₂, —CH═CH—CH₃, —C(═CH₂)—CH₃), propynyl (—CH—C≡CH, —C≡C—CH₃), 1,1-dimethylethyl, 1,1-dimethylpropyl, butenyl, butynyl, pentenyl and pentynyl, hexenyl and hexynyl.

For the purposes of this invention, the term “cycloalkyl” or “C₃₋₈ cycloalkyl” denotes cyclic hydrocarbons with 3, 4, 5, 6, 7 or 8 carbon atoms, wherein the hydrocarbons may be saturated or unsaturated (but not aromatic), unsubstituted or singly or multiply substituted. With respect to cycloalkyl, the term also comprises saturated or unsaturated (but not aromatic) cycloalkyls, in which one or two carbon atoms are replaced by an S, N or O heteroatom. C₃₋₈ cycloalkyl is advantageously selected from the group comprising cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclopentenyl, cyclohexenyl, cycloheptenyl and cyclooctenyl, but also tetrahydropyranyl, dioxanyl, dioxolanyl, morpholinyl, piperidinyl, piperazinyl, pyrazolinonyl and pyrrolidinyl.

The term “(CH₂)₃₋₆” denotes —CH₂—CH₂—CH₂—, —CH₂—CH₂—CH₂—CH₂—, —CH₂—CH₂—CH₂—CH₂—CH₂— and CH₂—CH₂—CH₂—CH₂—CH₂—CH₂—.

The term “aryl”, according to this invention, denotes carbocyclic ring systems comprising at least one aromatic ring, but without a heteroatom in only one of the rings, inter alia phenyls, naphthyls and phenanthrenyls, fluoranthenyls, fluorenyls, indanyls and tetralinyls. The aryl radicals can also be condensed with further saturated, (partially) unsaturated or aromatic ring systems. Each aryl radical can be present unsubstituted or singly or multiply substituted, wherein the aryl substituents may be the same or different and in any desired and possible position of the aryl. Phenyl or naphthyl radicals are particularly advantageous.

The term “heteroaryl” represents a 5-, 6- or 7-membered cyclic aromatic radical, which contains at least 1 heteroatom, optionally also 2, 3, 4 or 5 heteroatoms, wherein the heteroatoms may be the same or different and the heterocycle may be unsubstituted or singly or multiply substituted; in the case of substitution on the heterocycle, the substituents may be the same or different and in any desired and possible position of the heteroaryl. The heterocycle may also be part of a bi- or polycyclic system. Preferred heteroatoms are nitrogen, oxygen and sulphur. It is preferred for the heteroaryl radical to be selected from the group comprising pyrrolyl, indolyl, furyl (furanyl), benzofuranyl, thienyl (thiophenyl), benzothienyl, benzothiadiazolyl, benzothiazolyl, benzotriazolyl, benzodioxolanyl, benzodioxanyl, phthalazinyl, pyrazolyl, imidazolyl, thiazolyl, oxazolyl, isoxazoyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, pyranyl, indazolyl, purinyl, indolizinyl, quinolinyl, isoquinolinyl, quinazolinyl, carbazolyl, phenazinyl, phenothiazinyl or oxadiazolyl, wherein the binding with the compounds of general structure I can be made via any desired and possible ring member of the heteroaryl radical.

In conjunction with “alkyl”, the term “substituted”, according to this invention, denotes substitution of one or more hydrogen radicals by F, CI, Br, I, —CN, ═O, ═S, NH₂, NH-alkyl, NH-aryl, NH-heteroaryl, NH-cycloalkyl, NH-alkyl-aryl, NH-alkyl-heteroaryl, NH-alkyl-OH, N(alkyl)₂, N(alkyl-aryl)₂, N(alkyl-heteroaryl)₂, N(cycloalkyl)₂, N(alkyl-OH)₂, NH(C═O)alkyl, NH(C═O)aryl, NO₂, SH, S-alkyl, S-aryl, S-heteroaryl, S-alkyl-aryl, S-alkyl-heteroaryl, S-cycloalkyl, S-alkyl-OH, S-alkyl-SH, OH, O-alkyl, O-aryl, O-heteroaryl, O-alkyl-aryl, O-alkyl-heteroaryl, O-cycloalkyl, O-alkyl-OH, CHO, C(═O)C₁₋₆ alkyl, C(═S)C₁₋₆ alkyl, C(═O)aryl, C(═S)aryl, C(═O)C₁₋₆ alkyl-aryl, C(═S)C₁₋₆-alkyl aryl, C(═O)-heteroaryl, C(═S)-heteroaryl, C(═O)-cycloalkyl, C(═S)-cycloalkyl, CO₂H, CO₂-alkyl, CO₂-alkyl-aryl, C(═O)NH₂, C(═O)NH-alkyl, C(═O)NH-aryl, C(═O)NH-cycloalkyl, C(═O)N(alkyl)₂, C(═O)N(alkyl-aryl)₂, C(═O)N(alkyl-heteroaryl)₂, C(═O)N(cycloalkyl)₂, SO-alkyl, SO₂-alkyl, SO₂NH₂, SO₃H, PO(O—C₁₋₆ alkyl)₂, cycloalkyl, aryl or heteroaryl, wherein the term “multiply substituted radicals” denotes radicals that have been multiply substituted, for example twice or three times, either on different or on the same atoms, for example three times on the same C atom, as in the case of CF₃ or —CH₂CF₃, or in various positions, as in the case of —CH(OH)—CH═CH—CHCl₂. Multiple substitution can take place with the same substituent or with different substituents. A substituent may optionally also be substituted for its part; thus —O-alkyl also includes inter alia —O—CH₂—CH₂—O—CH₂—CH₂—OH.

With respect to “aryl”, “heteroaryl” and “cycloalkyl”, according to this invention, “singly or multiply substituted” denotes the single or multiple, for example double, treble, quadruple or quintuple, substitution of one or more hydrogen atoms of the ring system by F, CI, Br, I, CN, NH₂, NH-alkyl, NH-aryl, NH-heteroaryl, NH-alkyl-aryl, NH-alkyl-heteroaryl, NH-cycloalkyl, NH-alkyl-OH, N(alkyl)₂, N(alkyl-aryl)₂, N(alkyl-heteroaryl)₂, N(cycloalkyl)₂, N(alkyl-OH)₂, NO₂, SH, S-alkyl, S-cycloalkyl, S-aryl, S-heteroaryl, S-alkyl-aryl, S-alkyl-heteroaryl, S-cycloalkyl, S-alkyl-OH, S-alkyl-SH, OH, O-alkyl, O-cycloalkyl, O-aryl, O-heteroaryl, O-alkyl-aryl, O-alkyl-heteroaryl, O-cycloalkyl, O-alkyl-OH, CHO, C(═O)C₁₋₆ alkyl, C(═S)C₁₋₆ alkyl, C(═O)aryl, C(═S)aryl, C(═O)—C₁₋₆ alkyl-aryl, C(═S)C₁₋₆ alkyl-aryl, C(═O)-heteroaryl, C(═S)-heteroaryl, C(═O)-cycloalkyl, C(═S)-cycloalkyl, CO₂H, CO₂-alkyl, CO₂-alkyl-aryl, C(═O)NH₂, C(═O)NH-alkyl, C(═O)NH-aryl, C(═O)NH-cycloalkyl, C(═O)N(alkyl)₂, C(═O)N(alkyl-aryl)₂, C(═O)N(alkyl-heteroaryl)₂, C(═O)N(cycloalkyl)₂, S(O)-alkyl, S(O)-aryl, SO₂-alkyl, SO₂-aryl, SO₂NH₂, SO₃H, CF₃, ═O, ═S;

alkyl, cycloalkyl, aryl and/or heteroaryl; on one atom or optionally on different atoms (wherein a substituent can, in turn, optionally be substituted). Multiple substitution takes place here using the same or different substituents.

The term “salt” denotes any form of the active ingredient according to this invention in which it assumes or is charged with an ionic form and is coupled to a counter ion (a cation or anion) or is in solution. This also includes complexes of the active ingredient with other molecules and ions, in particular complexes complexed by ionic interactions. In particular this denotes (and this is also a preferred embodiment of this invention) physiologically acceptable salts, in particular physiologically acceptable salts with cations or bases and physiologically acceptable salts with anions or acids or else a salt formed with a physiologically acceptable acid or physiologically acceptable cation.

The term “physiologically acceptable salt with anions or acids” denotes, in the context of this invention, salts of at least one of the compounds according to this invention—usually protonated, for example on nitrogen—as a cation with at least one anion which are physiologically acceptable—in particular when applied to humans and/or mammals. In the context of this invention this denotes, in particular, the salt formed with a physiologically acceptable acid, namely salts of the respective active ingredient with inorganic or organic acids which are physiologically acceptable—in particular when applied to humans and/or mammals. Examples of physiologically acceptable salts of specific acids include salts of: hydrochloric acid, hydrobromic acid, sulphuric acid, methane sulphonic acid, formic acid, acetic acid, oxalic acid, succinic acid, malic acid, tartaric acid, mandelic acid, fumaric acid, lactic acid, citric acid, glutamic acid, saccharic acid, monomethyl sebacic acid, 5-oxo-proline, hexane-1-sulphonic acid, nicotinic acid, 2-, 3- or 4-amino benzoic acid, 2,4,6-trimethyl-benzoic acid, α-lipoic acid, acetyl glycine, phosphoric acid, maleic acid, malonic acid, hippuric acid and/or aspartic acid. The hydrochloride salt, the citrate and the hemicitrate are particularly preferred.

The term “salt formed with a physiologically acceptable acid”, according to this invention, denotes salts of the respective active ingredient with inorganic or organic acids which are physiologically acceptable—in particular when applied to humans and/or mammals. The hydrochloride and the citrate are particularly preferred. Examples of physiologically acceptable acids include: hydrochloric acid, hydrobromic acid, sulphuric acid, methane sulphonic acid, formic acid, acetic acid, oxalic acid, succinic acid, tartaric acid, mandelic acid, fumaric acid, lactic acid, citric acid, glutamic acid, saccharic acid, monomethyl sebacic acid, 5-oxo-proline, hexane-1-sulphonic acid, nicotinic acid, 2-, 3- or 4-amino benzoic acid, 2,4,6-trimethyl-benzoic acid, α-lipoic acid, acetyl glycine, hippuric acid and/or aspartic acid.

The term “physiologically acceptable salt with cations or bases” denotes, in the context of this invention, salts of at least one of the compounds according to this invention—usually a (deprotonated) acid—as an anion with at least one, preferably inorganic, cation, which are physiologically acceptable, in particular when applied to humans and/or mammals. The salts of the alkali and alkaline-earth metals are particularly preferred, but also ammonium salts, in particular (mono-) or (di-) sodium, (mono-) or (di-)potassium, magnesium or calcium salts.

The term “salt formed with a physiologically acceptable cation” denotes, according to this invention, salts of at least one of the respective compounds as an anion with at least one inorganic cation, which are physiologically acceptable, in particular when applied to humans and/or mammals. The salts of the alkali and alkaline-earth metals are particularly preferred, but also ammonium salts, in particular (mono-) or (di-) sodium, (mono-) or (di-)potassium, magnesium or calcium salts.

For a preferred embodiment of the substituted cyclohexyl-1,4-diamine derivatives according to the invention

R¹ and R² independently of one another represent H; saturated or unsaturated, branched or unbranched, singly or multiply substituted or unsubstituted C₁₋₅ alkyl;

or the radicals R¹ and R² together form a ring and represent CH₂CH₂OCH₂CH₂, CH₂CH₂NR¹⁰CH₂CH₂ or (CH₂)₃₋₆,

wherein R¹⁰ represents H; saturated or unsaturated, branched or unbranched, singly or multiply substituted or unsubstituted C₁₋₅ alkyl.

Particularly preferred are substituted cyclohexyl-1,4-diamine derivatives, wherein R¹ and R² independently of one another represent CH₃ or H, wherein R¹ and R² do not simultaneously represent H, or R¹ and R² represent CH₂CH₂OCH₂CH₂ or (CH₂)₆.

Also preferred are substituted cyclohexyl-1,4-diamine derivatives, wherein

R³ represents respectively unsubstituted or singly or multiply substituted cyclopentyl, cyclohexyl, phenyl, benzyl, naphthyl, anthracenyl, thiophenyl, benzothiophenyl, furyl, benzofuranyl, benzodioxolanyl, indolyl, indanyl, benzodioxanyl, pyrrolyl, pyridyl, pyrimidyl or pyrazinyl; respectively unsubstituted or singly or multiply substituted C₅₋₆ cycloalkyl, phenyl, naphthyl, anthracenyl, thiophenyl, benzothiophenyl, pyridyl, furyl, benzofuranyl, benzodioxolanyl, indolyl, indanyl, benzodioxanyl, pyrrolyl, pyrimidyl or pyrazinyl bound by a saturated, unbranched C₁₋₂ alkyl group;

in particular

R³ represents respectively unsubstituted or singly or multiply substituted phenyl, furyl, thiophenyl, naphthyl, benzyl, benzofuranyl, indolyl, indanyl, benzodioxanyl, benzodioxanyl, pyridyl, pyrimidyl, pyrazinyl or benzothiophenyl; respectively unsubstituted or singly or multiply substituted phenyl, furyl or thiophenyl bound by a saturated, unbranched C₁₋₂ alkyl group.

Particularly preferred are substituted cyclohexyl-1,4-diamine derivatives, wherein R³ represents respectively substituted or unsubstituted phenyl, thiophenyl, pyridyl or benzyl, particularly preferably 4-methylbenzyl, 3-chlorobenzyl, 4-chlorobenzyl, 3-methylbenzyl, benzyl, phenyl, thiophenyl and 3-fluorophenyl.

Substituted cyclohexyl-1,4-diamine derivatives wherein n represents 2 or 3 are preferred.

Substituted cyclohexyl-1,4-diamine derivatives wherein R⁴ represents

—(CR⁶R⁷)_(p)R⁸ and R⁵ represents H are also preferred.

Substituted cyclohexyl-1,4-diamine derivatives wherein R⁴ represents (CH₂)_(p)R⁸ and R⁵ represents —(CH₂)_(l)R⁸ are additionally preferred.

Substituted cyclohexyl-1,4-diamine derivatives wherein R⁴ and R⁵ together represent CH₂CHR¹⁴OCHR¹⁴CH₂, CH₂CH₂SCH₂CH₂, CH₂CH₂NR¹¹CH₂CH₂ (CR¹²R¹³)₃₋₆ or

are also preferred.

Substituted cyclohexyl-1,4-diamine derivatives wherein R⁶ represents H and R⁷ represents H, CH₃, unsubstituted or singly or multiply substituted benzyl, or COOR⁹ or R⁶ and R⁷ form a ring (CH₂)_(k)CHR⁸(CH₂)_(m) are also preferred.

Substituted cyclohexyl-1,4-diamine derivatives wherein R⁸ represents respectively saturated or unsaturated, branched or unbranched, unsubstituted or singly or multiply substituted C₁₋₆ alkyl; respectively unsubstituted or singly or multiply substituted cyclobutyl, cyclopropyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, anthracenyl, indolyl, naphthyl, benzofuranyl, benzothiophenyl, indanyl, benzodioxanyl, benzodioxolanyl, acenaphthyl, carbazolyl, phenyl, thiophenyl, furyl, pyrrolidinyl, tetrahydrofuryl, piperazinyl, pyridyl, pyrrolyl, pyrazinyl or pyrimidyl, fluorenyl, fluoranthenyl, benzothiazolyl, benzotriazolyl or benzo[1,2,5]thiazolyl or 1,2-dihydroacenaphthenyl, pyridinyl, furanyl, benzofuranyl, pyrazolinonyl, oxopyrazolinonyl, dioxolanyl, adamantyl, pyrimidinyl, quinolinyl, isoquinolinyl, phthalazinyl or quinazolinyl are also preferred.

Substituted cyclohexyl-1,4-diamine derivatives wherein R⁸ represents respectively saturated or unsaturated, branched or unbranched, unsubstituted or singly or multiply substituted C₁₋₆ alkyl; respectively unsubstituted or singly or multiply substituted pyrrolidinyl, morpholinyl, tetrahydrofuryl, tetrahydronaphthyl, dihydroindolyl, pyridyl, thienyl, piperazinyl, naphthyl, indanyl, quinolinyl, cyclopropyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, adamantyl, furyl, benzofuryl, phenyl or indolyl are particularly preferred.

Most preferred are substituted cyclohexyl-1,4-diamine derivatives from the group comprising

-   N-[1-(2,6-dichloro-benzyl)-pyrrolidin-3-yl]-N′-[4-dimethylamino-4-(4-methyl-benzyl)-cyclohexyl]-succinamide -   N-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-(2-oxo-tetrahydro-furan-3-yl)-succinamide -   N-[4-(4-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-(3,3-diphenyl-propyl)-succinamide -   N-[4-dimethylamino-4-(4-methyl-benzyl)-cyclohexyl]-4-[4-(7-methoxy-benzo[1,3]dioxol-5-ylmethyl)-piperazin-1-yl]-4-oxo-butyramide -   N-[4-(4-chloro-benzyl)-4-dimethylamino-cyclohexyl]-4-(3,6-dihydro-2H-pyridin-1-yl)-4-oxo-butyramide -   N-[4-dimethylamino-4-(4-methyl-benzyl)-cyclohexyl]-4-oxo-4-(4-m-tolyl-piperazin-1-yl)-butyramide -   2-{3-[4-(4-chloro-benzyl)-4-dimethylamino-cyclohexylcarbamoyl]-propionylamino}-propanoic     acid ethylester -   N-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-4-(8-fluoro-1,3,4,5-tetrahydro-pyrido[4,3-b]indol-2-yl)-4-oxo-butyramide -   3-{3-[4-dimethylamino-4-(4-methyl-benzyl)-cyclohexylcarbamoyl]-propionylamino}-propanoic     acid ethylester -   N-[4-dimethylamino-4-(4-methyl-benzyl)-cyclohexyl]-4-[4-(5-methyl-pyrazin-2-carbonyl)-piperazin-1-yl]-4-oxo-butyramide -   N-[4-dimethylamino-4-(4-methyl-benzyl)-cyclohexyl]-N′-methyl-N′-[2-(2,2,2-trifluoro-acetylamino)-ethyl]-succinamide -   N-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-(2-pyridin-2-yl-ethyl)-succinamide -   N-[4-(4-chloro-benzyl)-4-dimethylamino-cyclohexyl]-4-oxo-4-thiomorpholin-4-yl-butyramide -   N-[4-(4-chloro-benzyl)-4-dimethylamino-cyclohexyl]-4-[4-(5-methyl-pyrazin-2-carbonyl)-piperazin-1-yl]-4-oxo-butyramide -   N-[4-dimethylamino-4-(3-methyl-benzyl)-cyclohexyl]-N′-(2-thiophen-2-yl-ethyl)-succinamide -   N-[4-(4-chloro-benzyl)-4-dimethylamino-cyclohexyl]-4-[4-(4-ethoxy-phenyl)-piperazin-1-yl]-4-oxo-butyramide -   N-allyl-N′-[4-(4-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N-methyl-succinamide -   5-[4-(2,5-dimethoxy-benzyl)-piperazin-1-yl]-5-oxo-valeric acid     (4-benzyl-4-dimethylamino-cyclohexyl)-amide -   4-(3,6-dihydro-2H-pyridin-1-yl)-N-[4-dimethylamino-4-(4-methyl-benzyl)-cyclohexyl]-4-oxo-butyramide -   N-[4-dimethylamino-4-(3-methyl-benzyl)-cyclohexyl]-4-(4-methyl-piperidin-1-yl)-4-oxo-butyramide -   N-[4-dimethylamino-4-(4-methyl-benzyl)-cyclohexyl]-4-oxo-4-(4-pyridin-2-yl-piperazin-1-yl)-butyramide -   ({3-[4-dimethylamino     -4-(3-methyl-benzyl)-cyclohexylcarbamoyl]-propionyl}-methyl-amino)-acetic     acid benzyl ester -   4-[4-(2,6-dichloro-benzyl)-piperazin-1-yl]-N-[4-dimethylamino-4-(3-methyl-benzyl)-cyclohexyl]-4-oxo-butyramide -   {[4-(4-benzyl-4-dimethylamino-cyclohexylcarbamoyl)-butyryl]-methyl-amino}-acetic     acid tert butyl ester -   5-[4-(2-fluoro-5-methoxy-benzyl)-piperazin-1-yl]-5-oxo-valeric acid     (4-benzyl-4-dimethylamino-cyclohexyl)-amide -   N-[4-(4-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-(3-methoxy-propyl)-succinamide -   4-[4-(4-acetyl-phenyl)-piperazin-1-yl]-N-[4-dimethylamino-4-(4-methyl-benzyl)-cyclohexyl]-4-oxo-butyramide -   4-{3-[4-dimethylamino-4-(4-methyl-benzyl)-cyclohexylcarbamoyl]-propionyl}-piperazin-1-carboxylic     acid-tert-butylester -   N-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-(tetrahydro-furan-2-ylmethyl)-succinamide -   2-{3-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexylcarbamoyl]-propionylamino}-propanoic     acid ethylester -   N-(3-bromo-benzyl)-N′-[4-dimethylamino-4-(3-methyl-benzyl)-cyclohexyl]-succinamide -   3-(4-chloro-phenyl)-2-{3-[4-dimethylamino-4-(4-methyl-benzyl)-cyclohexylcarbamoyl]-propionylamino}-propanoic     acid methylester -   N-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-4-[4-(5-methyl-pyrazin-2-carbonyl)-piperazin-1-yl]-4-oxo-butyramide -   N-[4-(4-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-naphthalen-1-ylmethyl-succinamide -   N-[4-dimethylamino-4-(3-methyl-benzyl)-cyclohexyl]-4-[4-(3-fluoro-4-methoxy-benzyl)-piperazin-1-yl]-4-oxo-butyramide -   N-[4-dimethylamino-4-(4-methyl-benzyl)-cyclohexyl]-N′-[2-(1H-indol-3-yl)-ethyl]-N′-methyl-succinamide -   (4-{3-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexylcarbamoyl]-propionylamino}-benzyl)-phosphonic     acid diethylester -   N-[4-dimethylamino-4-(4-methyl-benzyl)-cyclohexyl]-N′-methyl-N′-(2-pyridin-2-yl-ethyl)-succinamide -   N-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-4-(3,6-dihydro-2H-pyridin-1-yl)-4-oxo-butyramide -   N-[4-dimethylamino-4-(3-methyl-benzyl)-cyclohexyl]-N′-(1-methyl-3-phenyl-propyl)-succinamide -   5-[4-(5-methyl-pyrazin-2-carbonyl)-piperazin-1-yl]-5-oxo-valeric     acid (4-benzyl-4-dimethylamino-cyclohexyl)-amide -   N-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-(2-chloro-6-methyl-benzyl)-succinamide -   N-allyl-N′-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N-methyl-succinamide -   N-[4-(4-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-cyclopentyl-succinamide -   N-[4-dimethylamino-4-(4-methyl-benzyl)-cyclohexyl]-N′-(tetrahydro-furan-2-ylmethyl)-succinamide -   (4-{3-[4-dimethylamino-4-(3-methyl-benzyl)-cyclohexylcarbamoyl]-propionylamino}-benzyl)-phosphonic     acid diethylester -   N-[4-(4-chloro-benzyl)-4-dimethylamino-cyclohexyl]-4-[4-(2-methoxy-phenyl)-piperazin-1-yl]-4-oxo-butyramide -   N-[4-dimethylamino-4-(3-methyl-benzyl)-cyclohexyl]-4-[4-(3-methoxy-phenyl)-piperazin-1-yl]-4-oxo-butyramide -   N-[4-(4-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-(3,5-difluoro-benzyl)-succinamide -   N-[4-(4-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-(2-methyl-benzyl)-succinamide -   N-[4-dimethylamino-4-(4-methyl-benzyl)-cyclohexyl]-4-oxo-4-{4-[(2,2,2-trifluoro-acetylamino)-methyl]-piperidin-1-yl}-butyramide -   N-[4-(4-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-[2-(1H-indol-3-yl)-ethyl]-succinamide -   N-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-[2-(1H-indol-3-yl)-ethyl]-N′-methyl-succinamide -   5-[4-(7-methoxy-benzo[1,3]dioxol-5-ylmethyl)-piperazin-1-yl]-5-oxo-valeric     acid (4-benzyl-4-dimethylamino-cyclohex)/l)-amide -   N-benzyl-N′-[4-dimethylamino-4-(3-methyl-benzyl)-cyclohexyl]-N-(2-hydroxy-ethyl)-succinamide -   5-[4-(2,3-dimethyl-phenyl)-piperazin-1-yl]-5-oxo-valeric acid     (4-benzyl-4-dimethylamino-cyclohexyl)-amide -   N-[4-(4-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-[2-(1H-indol-3-yl)-ethyl]-N′-methyl-succinamide -   N-[4-dimethylamino-4-(4-methyl-benzyl)-cyclohexyl]-4-[4-(2,3-dimethyl-phenyl)-piperazin-1-yl]-4-oxo-butyramide -   Glutaric acid-(4-benzyl-4-dimethylamino-cyclohexyl)-amide     (1,2,3,4-tetrahydro-naphthalen-1-yl)-amide -   N-[4-(4-chloro-benzyl)-4-dimethylamino-cyclohexyl]-4-(4-methyl-piperidin-1-yl)-4-oxobutyramide -   2-{3-[4-dimethylamino-4-(4-methyl-benzyl)-cyclohexylcarbamoyl]-propionylamino}-propanoic     acid-tert-butylester -   5-(4-cycloheptyl-piperazin-1-yl)-5-oxo-valeric acid     (4-benzyl-4-dimethylamino-cyclohexyl)-amide -   Glutaric acid-(4-benzyl-4-dimethylamino-cyclohexyl)-amide     [2-(4-fluoro-phenyl)-ethyl]-amide -   Glutaric acid-(4-benzyl-4-dimethylamino-cyclohexyl)-amide     [1-(2,6-dichloro-benzyl)-pyrrolidin-3-yl]-amide -   N-[4-(4-chloro-benzyl)-4-dimethylamino-cyclohexyl]-4-(1,4-dioxa-8-aza-spiro[4.5]dec-8-yl)-4-oxo-butyramide -   N-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-4-oxo-4-thiomorpholin-4-yl-butyramide -   4-(4-benzoyl-piperidin-1-yl)-N-[4-dimethylamino-4-(3-methyl-benzyl)-cyclohexyl]-4-oxo-butyramide -   N-[4-(4-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-(2,4-dimethoxy-benzyl)-succinamide -   N-[4-dimethylamino-4-(3-methyl-benzyl)-cyclohexyl]-N′-(1,2,3,4-tetrahydro-naphthalen-1-yl)-succinamide -   N-[4-(4-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-ethyl-N′-pyridin-4-ylmethyl-succinamide -   N-[2-(3,4-dimethoxy-phenyl)-ethyl]-N′-[4-dimethylamino-4-(3-methyl-benzyl)-cyclohexyl]-N-methyl-succinamide -   N-[4-(4-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-methyl-N′-pyridin-3-ylmethyl-succinamide -   N-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-pyridin-2-ylmethyl-succinamide -   N-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-(2-methyl-benzyl)-succinamide -   N-[4-dimethylamino-4-(3-methyl-benzyl)-cyclohexyl]-N′-(4-methoxy-phenyl)-succinamide -   N-[4-dimethylamino-4-(3-methyl-benzyl)-cyclohexyl]-N′-indan-2-yl-succinamide -   N-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-(1-methyl-3-phenyl-propyl)-succinamide -   N-(2-chloro-6-methyl-benzyl)-N′-[4-dimethylamino     -4-(3-methyl-benzyl)-cyclohexyl]-succinamide -   N-[4-dimethylamino-4-(4-methyl-benzyl)-cyclohexyl]-4-[4-(4-methoxy-phenyl)-piperazin-1-yl]-4-oxo-butyramide -   N-[4-dimethylamino-4-(4-methyl-benzyl)-cyclohexyl]-N′-[2-(4-fluoro-phenyl)-ethyl]-succinamide -   Glutaric acid-(4-benzyl-4-dimethylamino-cyclohexyl)-amide     4-dimethylamino-benzylamide -   N-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-(3,5-dichloro-benzyl)-succinamide -   N-[4-(4-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-(1-methyl-3-phenyl-propyl)-succinamide -   4-{3-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexylcarbamoyl]-propionyl}-piperazin-1-carboxylic     acid ethylester -   N-[4-dimethylamino-4-(3-methyl-benzyl)-cyclohexyl]-N′-(4-methoxy-benzyl)-succinamide -   N-[4-(4-chloro-benzyl)-4-dimethylamino-cyclohexyl]-4-(2,6-dimethyl-morpholin-4-yl)-4-oxo-butyramide -   N-[4-dimethylamino-4-(4-methyl-benzyl)-cyclohexyl]-4-oxo-4-(4-phenyl-3,6-dihydro-2H-pyridin-1-yl)-butyramide -   N-[4-(4-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-[2-(3-fluoro-phenyl)-ethyl]-succinamide -   4-[4-(4-allyloxy-benzyl)-piperazin-1-yl]-N-[4-dimethylamino-4-(3-methyl-benzyl)-cyclohexyl]-4-oxo-butyramide -   Glutaric acid-(4-benzyl-4-dimethylamino-cyclohexyl)-amide     [2-(5-bromo-2-methoxy-phenyl)-ethyl]-amide -   5-[4-(3-methoxy-phenyl)-piperazin-1-yl]-5-oxo-valeric acid     (4-benzyl-4-dimethylamino-cyclohexyl)-amide -   N-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-4-(4-methyl-piperidin-1-yl)-4-oxo-butyramide -   (4-{3-[4-(4-chloro-benzyl)-4-dimethylamino-cyclohexylcarbamoyl]-propionylamino}-benzyl)-phosphonic     acid diethylester -   N-[4-dimethylamino-4-(4-methyl-benzyl)-cyclohexyl]-4-oxo-4-(4-o-tolyl-piperazin-1-yl)-butyramide -   N-[4-dimethylamino-4-(3-methyl-benzyl)-cyclohexyl]-N′-[2-(3-fluoro-phenyl)-ethyl]-succinamide -   4-[4-(4-chloro-phenyl)-piperazin-1-yl]-N-[4-dimethylamino-4-(4-methyl-benzyl)-cyclohexyl]-4-oxo-butyramide -   N-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-[1-(4-fluoro-phenyl)-ethyl]-succinamide -   N-[4-(4-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-[1-(4-trifluoromethyl-benzyl)-pyrrolidin-3-yl]-succinamide -   N-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-[2-(1H-indol-3-yl)-ethyl]-succinamide -   N-[4-(4-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-indan-5-yl-succinamide -   N-(4-benzyloxy-phenyl)-N′-[4-dimethylamino-4-(4-methyl-benzyl)-cyclohexyl]-succinamide -   2-{3-[4-dimethylamino-4-(3-methyl-benzyl)-cyclohexylcarbamoyl]-propionylamino}-3-methyl-valeric     acid tert-butyl ester -   4-(4-benzyl-piperidin-1-yl)-N-[4-dimethylamino-4-(3-methyl-benzyl)-cyclohexyl]-4-oxo-butyramide -   N-[4-(4-chloro-benzyl)-4-dimethylamino-cyclohexyl]-4-[4-(4-fluoro-phenyl)-3,6-dihydro-2H-pyridin-1-yl]-4-oxo-butyramide -   N-[4-dimethylamino-4-(4-methyl-benzyl)-cyclohexyl]-N′-(1,2-dimethyl-propyl)-succinamide -   N-[4-dimethylamino-4-(3-methyl-benzyl)-cyclohexyl]-4-(8-fluoro-1,3,4,5-tetrahydro-pyrido[4,3-b]indol-2-yl)-4-oxo-butyramide -   4-[4-(3-chloro-benzoyl)-piperazin-1-yl]-N-[4-dimethylamino-4-(3-methyl-benzyl)-cyclohexyl]cyclohexyl]-4-oxo-butyramide -   N-[4-(4-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-(4-methoxy-phenyl)-succinamide -   5-[4-(2,6-dichloro-benzyl)-piperazin-1-yl]-5-oxo-valeric acid     (4-benzyl-4-dimethylamino-cyclohexyl)-amide -   N-[4-dimethylamino-4-(3-methyl-benzyl)-cyclohexyl]-N′-[2-(1H-indol-3-yl)-ethyl]-N′-methyl-succinamide -   N-[4-dimethylamino-4-(3-methyl-benzyl)-cyclohexyl]-N′-[1-(4-fluoro-phenyl)-ethyl]-succinamide -   4-[4-(4-chloro-phenyl)-piperazin-1-yl]-N-[4-dimethylamino-4-(3-methyl-benzyl)-cyclohexyl]-4-oxo-butyramide -   N-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-4-oxo-4-(4-oxo-1-phenyl-1,3,8-triaza-spiro     [4.5]dec-8-yl)-butyramide -   N-benzyl-N′-[4-dimethylamino-4-(3-methyl-benzyl)-cyclohexyl]-N-methyl-succinamide -   N-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-(3,5-difluoro-benzyl)-succinamide -   N-[4-dimethylamino-4-(3-methyl-benzyl)-cyclohexyl]-N′-[2-(4-fluoro-phenyl)-ethyl]-succinamide -   N-[4-dimethylamino-4-(3-methyl-benzyl)-cyclohexyl]-N′-[2-(1H-indol-3-yl)-ethyl]-succinamide -   N-(2-benzylsulphanyl-ethyl)-N′-[4-dimethylamino     -4-(3-methyl-benzyl)-cyclohexyl]-succinamide -   N-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-(2,4-difluoro-benzyl)-succinamide -   N-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-phenethyl-succinamide -   N-[4-dimethylamino-4-(3-methyl-benzyl)-cyclohexyl]-N′-(1-naphthalen-2-yl-ethyl)-succinamide -   N-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-(1-methoxymethyl-2-phenyl-ethyl)-succinamide -   N-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-(3,4-dichloro-benzyl)-succinamide -   N-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-furan-2-ylmethyl-succinamide -   N-[4-dimethylamino-4-(4-methyl-benzyl)-cyclohexyl]-N′-(1,2,3,4-tetrahydro-naphthalen-1-yl)-succinamide -   N-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-(4-fluoro-benzyl)-succinamide -   N-[4-dimethylamino-4-(3-methyl-benzyl)-cyclohexyl]-N′-indan-1-yl-succinamide -   N-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-4-(3,5-dimethyl-piperidin-1-yl)-4-oxo-butyramide -   N-[4-dimethylamino-4-(3-methyl-benzyl)-cyclohexyl]-N′-phenethyl-succinamide -   N-[4-dimethylamino-4-(4-methyl-benzyl)-cyclohexyl]-N′-phenethyl-succinamide -   N-(2-benzylsulphanyl-ethyl)-N′-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-succinamide -   N-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-(2,5-dichloro-benzyl)-succinamide -   4-[4-(3-chloro-benzoyl)-piperazin-1-yl]-N-[4-(4-chloro-benzyl)-4-dimethylamino-cyclohexyl]-4-oxo-butyramide -   N-[4-(4-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-(1-phenyl-propyl)-succinamide -   N-(4-bromo-2-fluoro-benzyl)-N′-[4-dimethylamino-4-(3-methyl-benzyl)-cyclohexyl]-succinamide -   N-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-methyl-N′-pyridin-3-ylmethyl-succinamide -   N-[4-dimethylamino-4-(4-methyl-benzyl)-cyclohexyl]-N′-(2-ethoxy-benzyl)-succinamide -   N-[4-dimethylamino-4-(3-methyl-benzyl)-cyclohhexyl]-N′-[2-(5-methoxy-1H-indol-3-yl)-ethyl]-succinamide -   N-(4-sec-butyl-phenyl)-N′-[4-(4-chloro-benzyl)-4-dimethylamino-cyclohexyl]-succinamide -   5-oxo-5-(4-phenyl-3,6-dihydro-2H-pyridin-1-yl)-valeric acid     (4-benzyl-4-dimethylamino-cyclohexyl)-amide -   5-oxo-5-(4-phenyl-3,6-dihydro-2H-pyridin-1-yl)-valeric acid     (4-benzyl-4-dimethylamino-cyclohexyl)-amide -   N-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-[2-(3-fluoro-phenyl)-ethyl]-succinamide -   N-(3-bromo-benzyl)-N′-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-succinamide -   N-(4-bromo-2-fluoro-benzyl)-N′-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-succinamide -   N-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-(1-phenyl-propyl)-succinamide -   N-[4-dimethylamino-4-(3-methyl-benzyl)-cyclohexyl]-N′-(4-fluoro-2-trifluoromethyl-benzyl)-succinamide -   N-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-indan-2-yl-succinamide -   N-[4-dimethylamino-4-(3-methyl-benzyl)-cyclohexyl]-4-oxo-4-(4-phenyl-3,6-dihydro-2H-pyridin-1-yl)-butyramide -   N-[4-(4-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-[2-(2-fluoro-phenyl)-ethyl]-succinamide -   N-[4-dimethylamino-4-(4-methyl-benzyl)-cyclohexyl]-N′-[2-(2-fluoro-phenyl)-ethyl]-succinamide -   Glutaric acid-(4-benzyl-4-dimethylamino-cyclohexyl)-amide     [2-(2-fluoro-phenyl)-ethyl]-amide -   N-[2-(2-chloro-phenyl)-ethyl]-N′-[4-dimethylamino-4-(4-methyl-benzyl)-cyclohexyl]-succinamide -   N-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-(3,4-difluoro-benzyl)-succinamide -   N-benzyl-N-(2-cyano-ethyl)-N′-[4-dimethylamino-4-(4-methyl-benzyl)-cyclohexyl]-succinamide -   N-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-(3-methyl-benzyl)-succinamide -   N-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-(4-fluoro-3-trifluoromethyl-benzyl)-succinamide -   N-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-[2-(2-chloro-phenyl)-ethyl]-succinamide -   N-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-[2-(4-chloro-phenyl)-ethyl]-succinamide -   N-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-[2-(2,4-dichloro-phenyl)-ethyl]-succinamide -   N-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-indan-1-yl-succinamide -   N-[4-(4-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-indan-1-yl-succinamide -   N-[2-(4-chloro-phenyl)-propyl]-N′-[4-dimethylamino-4-(3-methyl-benzyl)-cyclohexyl]-succinamide -   N-(3-bromo-benzyl)-N′-[4-(4-chloro-benzyl)-4-dimethylamino-cyclohexyl]-succinamide -   N-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-(3-phenyl-propyl)-succinamide -   N-[4-dimethylamino-4-(4-methyl-benzyl)-cyclohexyl]-N′-(2-p-tolyl-ethyl)-succinamide -   N-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-(2-thiophen-2-yl-ethyl)-succinamide -   Glutaric acid-(4-benzyl-4-dimethylamino-cyclohexyl)-amide     [2-(4-chloro-phenyl)-propyl]-amide -   N-benzyl-N′-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N-methyl-succinamide -   N-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-[2-(3-chloro-phenyl)-ethyl]-succinamide -   Glutaric acid-(4-benzyl-4-dimethylamino-cyclohexyl)-amide     [2-(2-ethoxy-phenyl)-ethyl]-amide -   Glutaric acid-(4-benzyl-4-dimethylamino-cyclohexyl)-amide     phenethyl-amide -   Glutaric acid-(4-benzyl-4-dimethylamino-cyclohexyl)-amide     [2-(3-chloro-phenyl)-ethyl]-amide -   N-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-[1-(3-methoxy-phenyl)-ethyl]-succinamide -   Glutaric acid-(4-benzyl-4-dimethylamino-cyclohexyl)-amide     (1,3-dimethyl-butyl)-amide -   N-benzyl-N′-[4-dimethylamino-4-(3-methyl-benzyl)-cyclohexyl]-N-ethyl-succinamide -   N-(4-chloro-benzyl)-N′-[4-(3-chloro     -benzyl)-4-dimethylamino-cyclohexyl]-succinamide -   N-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-[2-(2-fluoro-phenyl)-ethyl]-succinamide -   N-[4-dimethylamino-4-(3-methyl-benzyl)-cyclohexyl]-N′-(2-fluoro-benzyl)-succinamide -   N-[2-(4-chloro-phenyl)-ethyl]-N′-[4-dimethylamino-4-(3-methyl-benzyl)-cyclohexyl]-succinamide -   N-[2-(2-chloro-phenyl)-ethyl]-N′-[4-dimethylamino-4-(3-methyl-benzyl)-cyclohexyl]-succinamide -   N-[2-(3-chloro-phenyl)-ethyl]-N′-[4-dimethylamino-4-(3-methyl-benzyl)-cyclohexyl]-succinamide -   N-benzyl-N′-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N-(2-cyano-ethyl)-succinamide -   N-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-(3-chloro-4-fluoro-benzyl)-succinamide -   N-[4-dimethylamino-4-(3-methyl-benzyl)-cyclohexyl]-N′-(2-trifluoromethyl-benzyl)-succinamide -   N-[2-(2,4-dichloro-phenyl)-ethyl]-N′-[4-dimethylamino-4-(3-methyl-benzyl)-cyclohexyl]-succinamide -   N-benzyl-N′-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N-ethyl-succinamide -   N-[2-(4-chloro-phenyl)-ethyl]-N′-[4-dimethylamino-4-(4-methyl-benzyl)-cyclohexyl]-succinamide -   5-oxo-5-(4-o-tolyl-piperazin-1-yl)-valeric acid     (4-benzyl-4-dimethylamino-cyclohexyl)-amide -   N-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-[3-(methyl-phenyl-amino)-propyl]-succinamide -   N-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-4-[4-(5-chloro-2-methyl-phenyl)-piperazin-1-yl]-4-oxo-butyramide -   N-[4-dimethylamino-4-(3-methyl-benzyl)-cyclohexyl]-N′-[2-(2-ethoxy-phenyl)-ethyl]-succinamide -   4-[4-(4-chloro-benzoyl)-piperidin-1-yl]-N-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-4-oxo-butyramide -   N-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-[2-(2-ethoxy-phenyl)-ethyl]-succinamide -   N-[2-(2,6-dichloro-phenyl)-ethyl]-N′-[4-dimethylamino-4-(3-methyl-benzyl)-cyclohexyl]-succinamide -   N-benzhydryl-N′-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-succinamide -   N-[4-(3-chloro     -benzyl)-4-dimethylamino-cyclohexyl]-N′-cyclooctyl-succinamide -   N-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-[2-(4-phenoxy-phenyl)-ethyl]-succinamide -   N-[4-dimethylamino-4-(3-methyl-benzyl)-cyclohexyl]-N′-(2,3-dimethyl-benzyl)-succinamide -   4-[4-(5-chloro-2-methyl-phenyl)-piperazin-1-yl]-N-[4-dimethylamino-4-(3-methyl-benzyl)-cyclohexyl]-4-oxo-butyramide -   4-[4-(4-chloro-benzoyl)-piperidin-1-yl]-N-[4-dimethylamino-4-(3-methyl-benzyl)-cyclohexyl]-4-oxo-butyramide -   N-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-(1,2,3,4-tetrahydro-naphthalen-1-yl)-succinamide -   N-(2-chloro-benzyl)-N′-[4-dimethylamino     -4-(3-methyl-benzyl)-cyclohexyl]-succinamide -   N-(2-chloro-benzyl)-N′-[4-(3     -chloro-benzyl)-4-dimethylamino-cyclohexyl]-succinamide -   N-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-(3-fluoro-5-trifluoromethyl-benzyl)-succinamide -   N-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-(1-p-tolyl-ethyl)-succinamide -   N-[2-(2,6-dichloro-benzylsulphanyl)-ethyl]-N′-[4-dimethylamino-4-(4-methyl-benzyl)-cyclohexyl]-succinamide -   N-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-[2-(2,6-dichloro-benzylsulphanyl)-ethyl]-succinamide -   N-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-[2-(3-trifluoromethyl-phenyl)-ethyl]-succinamide -   N-[2-(3,4-dichloro-phenyl)-ethyl]-N′-[4-dimethylamino-4-(3-methyl-benzyl)-cyclohexyl]-succinamide -   N-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-4-[4-(2-fluoro-phenyl)-piperazin-1-yl]-4-oxo-butyramide -   5-[4-(2,4-dimethoxy-phenyl)-piperazin-1-yl]-5-oxo-valeric acid     (4-benzyl-4-dimethylamino-cycloh -   N-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-(1-naphthalen-1-yl-ethyl)-succinamide -   N-[4-dimethylamino-4-(3-methyl-benzyl)-cyclohexyl]-N′-(1-naphthalen-1     -yl-ethyl)-succinamide -   N-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-(2-fluoro-benzyl)-N′-furan-2-ylmethyl-succinamide -   N-[4-dimethylamino-4-(3-methyl-benzyl)-cyclohexyl]-N′-(2-fluoro-benzyl)-N′-furan-2-ylmethyl-succinamide -   N-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-(2,5-dimethoxy-benzyl)-N′-furan-2-ylmethyl-succinamide -   N-(4-azepan-1-yl-4-benzyl-cyclohexyl)-4-(2,3-dihydro-indol-1-yl)-4-oxo-butyramide -   4-(2,3-dihydro-indol-1-yl)-N-[4-dimethylamino-4-(3-fluoro-phenyl)-cyclohexyl]-4-oxo-butyramide -   N-(4-benzyl-4-morpholin-4-yl-cyclohexyl)-N′-(2-chloro-6-methyl-benzyl)-succinamide -   N-(4-benzyl-4-morpholin-4-yl-cyclohexyl)-N′-[2-(3-methoxy-phenyl)-ethyl]-succinamide -   N-(4-benzyl-4-morpholin-4-yl-cyclohexyl)-N′-(3-methyl-benzyl)-succinamide -   N-(4-benzyl-4-morpholin-4-yl-cyclohexyl)-N′-(4-bromo-2-fluoro-benzyl)-succinamide -   N-(4-benzyl-4-morpholin-4-yl-cyclohexyl)-N′-pyridin-4-ylmethyl-succinamide -   N-(4-benzyl-4-morpholin-4-yl-cyclohexyl)-N′-indan-1-yl-succinamide -   N-(4-benzyl-4-morpholin-4-yl-cyclohexyl)-N′-(2,4-dimethoxy-benzyl)-succinamide -   N-(4-benzyl-4-morpholin-4-yl-cyclohexyl)-N′-thiophen-2-ylmethyl-succinamide -   N-adamantan-1-ylmethyl-N′-(4-benzyl-4-morpholin-4-yl-cyclohexyl)-succinamide -   N-(4-benzyl-4-morpholin-4-yl-cyclohexyl)-N′-(2,5-difluoro-benzyl)-succinamide -   N-(4-benzyl-4-morpholin-4-yl-cyclohexyl)-N′-(4-tert-butyl-phenyl)-succinamide -   N-(4-benzyl-4-morpholin-4-yl-cyclohexyl)-N′-(3,5-bis-trifluoromethyl-benzyl)-succinamide -   N-(4-benzyl-4-morpholin-4-yl-cyclohexyl)-N′-[2-(2-ethoxy-phenyl)-ethyl]-succinamide -   N-(4-benzyl-4-morpholin-4-yl-cyclohexyl)-N′-(3-methoxy-propyl)-succinamide -   N-(4-benzyl-4-morpholin-4-yl-cyclohexyl)-N′-(2-morpholin-4-yl-ethyl)-succinamide -   N-(4-benzyl-4-morpholin-4-yl-cyclohexyl)-N′-(2,5-dichloro-benzyl)-succinamide -   N-(4-benzyl-4-morpholin-4-yl-cyclohexyl)-N′-[1-(2-benzyloxy-benzyl)-pyrrolidin-3-yl]-N′-methyl-succinamide -   N-(4-benzyl-4-morpholin-4-yl-cyclohexyl)-4-oxo-4-(2-pyrrolidin-1-ylmethyl-pyrrolidin-1-yl)-butyramide -   N-(4-benzyl-4-morpholin-4-yl-cyclohexyl)-4-morpholin-4-yl-4-oxo-butyramide -   N-(4-benzyl-4-morpholin-4-yl-cyclohexyl)-N′-(3-dimethylamino-propyl)-N′-methyl-succinamide -   N-(4-benzyl-4-morpholin-4-yl-cyclohexyl)-N′-(2-phenyl-cyclopropyl)-succinamide -   N-(4-benzyl-4-morpholin-4-yl-cyclohexyl)-N′-naphthalen-1-ylmethyl-succinamide -   N-(4-benzyl-4-morpholin-4-yl-cyclohexyl)-4-(4-methyl-[1,4]diazepan-1-yl)-4-oxo-butyramide -   N-(4-benzyl-4-morpholin-4-yl-cyclohexyl)-4-(4-hydroxy-piperidin-1-yl)-4-oxo-butyramide -   N-(4-benzyl-4-morpholin-4-yl-cyclohexyl)-N′-[2-(7-methyl-1H-indol-3-yl)-ethyl]-succinamide -   N-(4-benzyl-4-morpholin-4-yl-cyclohexyl)-N′-[2-(5-methoxy-1H-indol-3-yl)-ethyl]-succinamide -   N-(4-benzyl-4-morpholin-4-yl-cyclohexyl)-4-oxo-4-(4-quinolin-2-ylmethyl-piperazin-1-yl)-butyramide -   N-(4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-4-oxo-4-[4-(5-trifluoromethyl-pyridin-2-yl)-piperazin-1-yl]-butyramide -   Glutaric acid-(1-adamantan-1-yl-ethyl)-amide     (4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-amide -   N-[2-(2,6-dichloro-phenyl)-ethyl]-N′-(4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-succinamide -   N-(4-dimethylamino-4-thi     thiophen-2-yl-cyclohexyl)-N′-(1-methyl-3-phenyl-propyl)-succinamide -   N-benzyl-N′-(4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-N-ethyl-succinamide -   N-[2 -(4-bromo-phenyl)-ethyl]-N′-(4-dimethylamino     -4-thiophen-2-yl-cyclohexyl)-succinamide -   4-[4-(4-chloro-benzoyl)-piperidin-1-yl]-N-(4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-4-oxo-butyramide -   Glutaric acid-[1-(2,6-dichloro-benzyl)-pyrrolidin-3-yl]-amide     (4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-amide -   Glutaric acid-(4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-amide     (3-phenyl-propyl)-amide -   N-(4-dimethylamino-4-phenyl-cyclohexyl)-N′-pentyl-succinamide -   3-(4-chloro-phenyl)-2-[4-(4-dimethylamino-4-thiophen-2-yl-cyclohexylcarbamoyl)-butyrylamino]-propanoic     acid ethylester -   Glutaric acid-(4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-amide     indan-1-ylamide -   N-adamantan-1-ylmethyl-N′-(4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-succinamide -   5-(4-benzofuran-2-ylmethyl-piperazin-1-yl)-5-oxo-valeric acid     (4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-amide -   4-[4-(4-tert-butyl-benzyl)-piperazin-1-yl]-N-(4-dimethylamino-4-phenyl-cyclohexyl)-4-oxo-butyramide -   Glutaric acid-(4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-amide     [2-(1H-indol-3-yl)-ethyl]-amide -   N-(4-dimethylamino-4-phenyl-cyclohexyl)-4-[4-hydroxy-4-(3-trifluoromethyl-phenyl)-piperidin-1-yl]-4-oxo-butyramide -   5-(3,4-dihydro-1H-isoquinolin-2-yl)-5-oxo-valeric acid     (4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-amide -   4-(4-benzyl-piperidin-1-yl)-N-(4-dimethylamino-4-phenyl-cyclohexyl)-4-oxo-butyramide -   {[4-(4-dimethylamino     -4-thiophen-2-yl-cyclohexylcarbamoyl)-butyryl]-methyl-amino}-acetic     acid benzylester -   N-benzyl-N′-(4-dimethylamino-4-phenyl-cyclohexyl)-N-phenethyl-succinamide -   Glutaric acid-(4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-amide     3-trifluoromethoxy-benzylamide -   Glutaric acid-(4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-amide     ethyl-(2-methyl-allyl)-amide -   N,N-bis-(2-cyano-ethyl)-N′-(4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-succinamide -   Glutaric acid-benzyl-methyl-amide     (4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-amide -   Glutaric acid-(2-benzyloxy-cyclopentyl)-amide     (4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-amide -   Glutaric acid-(4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-amide     4-trifluoromethyl-benzylamide -   N-(4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-N′-[2-(4-phenoxy-phenyl)-ethyl]-succinamide -   Glutaric acid-(4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-amide     (3,3-diphenyl-propyl)-amide -   4-(4-benzyl-piperidin-1-yl)-N-(4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-4-oxo-butyramide -   N-(4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-4-[4-hydroxy-4-(3-trifluoromethyl-phenyl)-piperidin-1-yl]-4-oxo-butyramide -   Glutaric acid-(4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-amide     4-fluoro-2-trifluoromethyl-benzylamide -   N-(4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-N′-pentyl-succinamide -   5-[4-(2-methoxy-naphthalen-1-ylmethyl)-piperazin-1-yl]-5-oxo-valeric     acid (4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-amide -   N-(4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-N′-(2-ethoxy-benzyl)-N′-furan-2-ylmethyl-succinamide -   Glutaric acid-(4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-amide     (2-phenyl-cyclopropyl)-amide -   N-[2-(3,4-dichloro-phenyl)-ethyl]-N′-(4-dimethylamino-4-phenyl-cyclohexyl)-succinamide -   N-adamantan-1-ylmethyl-N′-(4-dimethylamino-4-phenyl-cyclohexyl)-succinamide     5-[4-(4-fluoro-phenyl)-3,6-dihydro-2H-pyridin-1-yl]-5-oxo-valeric     acid (4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-amide -   2-[4-(4-dimethylamino-4-thiophen-2-yl-cyclohexylcarbamoyl)-butyrylamino]-4-methyl-valeric     acid benzyl ester -   {4-[4-(4-dimethylamino-4-thiophen-2-yl-cyclohexylcarbamoyl)-butyrylamino]-phenyl}-carbamic     acid-tert-butylester -   Glutaric acid-(4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-amide     [2-(3-methoxy-phenyl)-ethyl]-amide -   Glutaric acid-benzyl-ethyl-amide     (4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-amide -   Glutaric acid-3-chloro-benzylamide     (4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-amide -   Glutaric acid-(4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-amide     (4-methyl-cyclohexyl)-amide -   N-(4-dimethylamino-4-phenyl-cyclohexyl)-N′-[2-(1H-indol-3-yl)-ethyl]-N′-methyl-succinamide -   Glutaric acid-2,5-dichloro-benzylamide     (4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-amide -   Glutaric acid-(4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-amide     [2-(3-fluoro-phenyl)-ethyl]-amide -   N-(4-dimethylamino-4-phenyl-cyclohexyl)-N′-[2-(4-methoxy-phenoxy)-ethyl]-succinamide -   N-(4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-N′-[2-(ethyl-m-tolyl-amino)-ethyl]-succinamide -   Glutaric acid-(4-benzyloxy-phenyl)-amide     (4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-amide -   Glutaric acid-(4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-amide     [2-(4-fluoro-phenyl)-ethyl]-amide -   Glutaric acid-[2-(4-bromo-phenyl)-ethyl]-amide     (4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-amide -   N-(4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-N′-(4-phenoxy-phenyl)-succinamide -   N-(4-dimethylamino-4-phenyl-cyclohexyl)-N′-[2-(3-trifluoromethyl-phenyl)-ethyl]-succinamide -   Glutaric acid-[2-(4-chloro-phenyl)-propyl]-amide     (4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-amide -   N-(4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-N′-[2-(1H-indol-3-yl)-ethyl]-N′-methyl-succinamide -   N-(4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-N′-[2-(4-methoxy-phenoxy)-ethyl]-succinamide -   Glutaric acid-(4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-amide     (3-phenoxy-phenyl)-amide -   N-(4-dimethylamino-4-phenyl-cyclohexyl)-N′-[2-(ethyl-m-tolyl-amino)-ethyl]-succinamide -   Glutaric acid-[2-(5-bromo-2-methoxy-phenyl)-ethyl]-amide     (4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-amide -   N-(4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-N′-[2-(3-trifluoromethyl-phenyl)-ethyl]-succinamide -   Glutaric acid-(4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-amide     (1-methyl-3-phenyl-propyl)-amide -   N-[2-(2,6-dichloro-benzylsulphanyl)-ethyl]-N′-(4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-succinamide -   Glutaric acid-(4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-amide     (2,2-diphenyl-propyl)-amide -   N-(4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-N′-[3-(methyl-phenyl-amino)-propyl]-succinamide -   N-(1-biphenyl-4-ylmethyl-pyrrolidin-3-yl)-N′-(4-dimethylamino     -4-thiophen-2-yl-cyclohexyl)-N-methyl-succinamide -   Glutaric acid-[4-(cyano-phenyl-methyl)-phenyl]-amide     (4-dimethylamino-4-thiophen-2-ylcyclohexyl)-amide -   Glutaric acid-(4-tert-butyl-cyclohexyl)-amide     (4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-amide -   Glutaric acid-(4-sec-butyl-phenyl)-amide     (4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-amide -   Glutaric acid-(4-butyl-phenyl)-amide     (4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-amide -   N-(2-benzylsulphanyl-ethyl)-N′-(4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-succinamide -   N-(4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-N′-(2-phenoxy-ethyl)-succinamide -   Glutaric acid-(4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-amide     (naphthalen-1-ylmethyl)-amide -   Glutaric acid-3-bromo-benzylamide     (4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-amide -   N-(4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-N′-(3-phenyl-propyl)-succinamide -   N-[2-(3-chloro-phenyl)-ethyl]-N′-(4-dimethylamino-4-phenyl-cyclohexyl)-succinamide -   2-[3-(4-dimethylamino-4-thiophen-2-yl-cyclohexylcarbamoyl)-propionylamino]-propanoic     acid benzylester -   N-[2-(2-chloro-phenyl)-ethyl]-N′-(4-dimethylamino-4-phenyl-cyclohexyl)-succinamide -   N-(4-dimethylamino-4-phenyl-cyclohexyl)-N′-[2-(3-fluoro-phenyl)-ethyl]-succinamide -   Glutaric acid-(4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-amide     (2-thiophen-2-yl-ethyl)-amide -   Glutaric acid-(4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-amide     [2-(4-phenoxy-phenyl)-ethyl]-amide -   N-[2-(4-chloro-phenyl)-ethyl]-N′-(4-dimethylamino-4-phenyl-cyclohexyl)-succinamide -   N-[2-(3-chloro-phenyl)-ethyl]-N′-(4-dimethylamino     -4-thiophen-2-yl-cyclohexyl)-succinamide -   N-benzyl-N′-(4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-N-ethyl-succinamide -   Glutaric acid-[1-(2,6-dichloro-benzyl)-pyrrolidin-3-yl]-amide     (4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-amide -   Glutaric acid-(4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-amide     (3-phenyl-propyl)-amide -   Glutaric acid-(4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-amide     [2-(1H-indol-3-yl)-ethyl]-amide -   5-(3,4-dihydro-1H-isoquinolin-2-yl)-5-oxo-valeric acid     (4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-amide -   {[4-(4-dimethylamino-4-thiophen-2-yl-cyclohexylcarbamoyl)-butyryl]-methyl-amino}-acetic     acid benzylester -   N-(4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-N′-[2-(4-phenoxy-phenyl)-ethyl]-succinamide -   Glutaric acid-(4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-amide     (2-phenyl-cyclopropyl)-amide -   N-[4-(3-chlorobenzyl)-4-dimethylaminocyclohexyl]-N′-furan-2-ylmethylsuccinic     acid amide hydrochloride, non-polar diastereoisomer -   N-[4-(3-chlorobenzyl)-4-dimethylaminocyclohexyl]-N′-furan-2-ylmethylsuccinic     acid amide hydrochloride, polar diastereoisomer -   Glutaric acid (4-benzyl-4-dimethylaminocyclohexyl)amide     [2-(2-fluorophenyl)ethyl]amide hydrochloride, non-polar     diastereoisomer -   Glutaric acid (4-benzyl-4-dimethylaminocyclohexyl)amide     [2-(2-fluorophenyl)ethyl] amide hydrochloride, polar diastereoisomer -   N-[4-(3-chlorobenzyl)-4-dimethylaminocyclohexyl]-N′-[2-(4-chlorophenyl)ethyl]-succinic     acid amide hydrochloride, non-polar diastereoisomer -   N-[4-(3-chlorobenzyl)-4-dimethylaminocyclohexyl]-N′-[2-(4-chlorophenyl)ethyl]-succinic     acid amide hydrochloride, polar diastereoisomer -   Glutaric acid (4-benzyl-4-dimethylaminocyclohexyl)amide     [2-(4-chlorophenyl)ethyl]amide hydrochloride, non-polar     diastereoisomer

in the form of the racemate; the enantiomers, diastereomers, mixtures of the enantiomers or diastereomers or an individual enantiomer or diastereomer; the bases and/or salts of physiologically acceptable acids or cations.

The substances according to the invention act, for example, on the ORL1 receptor that is relevant in connection with various diseases, so they are suitable as a pharmaceutical active ingredient in a pharmaceutical composition. The invention therefore further relates to pharmaceutical compositions containing at least one substituted cyclohexyl carboxylic acid derivative according to the invention, and optionally suitable additives and/or auxiliaries and/or optionally further active ingredients.

The pharmaceutical compositions according to the invention contain, in addition to at least one substituted cyclohexyl-1,4-diamine derivative according to the invention, optionally suitable additives and/or auxiliaries, therefore also excipients, fillers, solvents, diluents, dyes and/or binders and can be administered as liquid pharmaceutical compositions in the form of injection solutions, drops or syrups, as semi-solid pharmaceutical compositions in the form of granules, tablets, pellets, patches, capsules, plasters or aerosols. The choice of auxiliaries, etc. and the amounts thereof to be used depend on whether the pharmaceutical composition is to be applied orally, perorally, parenterally, intravenously, intraperitoneally, intradermally, intramuscularly, intranasally, buccally, rectally or topically, for example to the skin, the mucous membranes or the eyes. Preparations in the form of tablets, dragees, capsules, granules, drops, juices and syrups are suitable for oral application, solutions, suspensions, easily reconstitutable dry preparations and sprays are suitable for parenteral, topical and inhalative applications. Substituted cyclohexyl-1,4-diamine derivatives according to the invention in a deposit, in dissolved form or in a plaster, optionally with the addition of agents to promote skin penetration, are suitable percutaneous application preparations. Orally or percutaneously applicable preparation forms can release the substituted cyclohexyl-1,4-diamine derivatives according to the invention after a delay. The substituted cyclohexyl-1,4-diamine derivatives according to the invention may also be applied in the form of parenteral long-acting repositories such as implants or implanted pumps. In principle, further active ingredients known to the person skilled in the art can be added to the pharmaceutical compositions according to the invention.

The amount of active ingredient to be administered to the patient varies as a function of the weight of the patient, the method of application, the indication and the severity of the illness. Conventionally, 0.00005 to 50 mg/kg, preferably 0.01 to 5 mg/kg, of at least one substituted cyclohexyl-1,4-diamine derivative according to the invention are applied.

For all of the above-mentioned forms of the pharmaceutical composition according to the invention, it is particularly preferred if, in addition to at least one substituted cyclohexyl-1,4-diamine derivative, the pharmaceutical composition contains a further active ingredient, in particular an opioid, preferably a strong opioid, in particular morphine, or an anaesthetic, preferably hexobarbital or halothane.

In a preferred form of the pharmaceutical composition, a contained substituted cyclohexyl-1,4-diamine derivative according to the invention is in the form of a pure diastereomer and/or enantiomer, as a racemate or as a non-equimolar or equimolar blend of the diastereomers and/or enantiomers.

Both the ORL1 receptor and the further opioid receptors have been identified in particular in the occurrence of pain. Accordingly, substituted cyclohexyl-1,4-diamine derivatives according to the invention can be used for producing a pharmaceutical composition for the treatment of pain, in particular acute, neuropathic or chronic pain.

The invention therefore further relates to the use of a substituted cyclohexyl-1,4-diamine derivative according to the invention for producing a pharmaceutical composition for treating pain, in particular acute, visceral, neuropathic or chronic pain.

The invention further relates to the use of a substituted cyclohexyl-1,4-diamine derivative according to the invention for the production of a pharmaceutical composition for the treatment of anxiety, stress and stress-related syndromes, depression, epilepsy, Alzheimer's disease, senile dementia, catalepsy, general cognitive dysfunction, learning and memory disorders (as a nootropic), withdrawal symptoms, alcohol- and/or drug- and/or medicine abuse and/or dependency, sexual dysfunction, cardiovascular diseases, hypotension, hypertension, tinnitus, pruritus, migraine, hearing difficulties, deficient intestine motility, impaired absorption of nutrients, anorexia, obesity, locomotive disorders, diarrhoea, cachexia, urinary incontinence, or as a muscle relaxant, anti-convulsive or anaesthetic or for co-administration in treatment with an opioid analgesic or anaesthetic, for diuresis or anti-natriuresis, anxiolysis, for modulation of motor activity, for modulation of neurotransmitter release and treatment of neurodegenerative diseases connected therewith, for the treatment of withdrawal symptoms and/or for reducing opioid addiction potential.

In this case it may be preferred in one of the present uses if a substituted cyclohexyl-1,4-diamine derivative used is in the form of a pure diastereomer and/or enantiomer, as a racemate or as a non-equimolar or equimolar blend of the diastereomers and/or enantiomers.

The invention further relates to a process for the treatment, in particular in one of the above-mentioned indications, of a non-human mammal or human, which or who requires treatment of pain, in particular chronic pain, by administration of a therapeutically effective dose of a substituted cyclohexyl-1,4-diamine derivative according to the invention, or of a pharmaceutical composition according to the invention.

The invention further relates to a process for producing the substituted cyclohexyl-1,4-diamine derivatives according to the invention, as stated in the following description and examples.

The radicals R⁰¹ and R⁰² have the meaning given for compounds according to the invention of formula I for R¹ and R² and, in addition, independently of one another can represent a protecting group. The remaining radicals have the meaning indicated in formula I:

Basically the various methods known to a person skilled in the art for producing amides are suitable for preparing the diamides according to the invention. The process according to the invention involves linking substituted cyclohexane-1,4-diamines (WO 02090317) via anhydrides, open-chain dicarboxylic acids or preferably the activated analogues thereof, in particular the acid halides thereof, with further primary or secondary amines and thus converting them into compounds according to the invention. Preferably anhydrides are initially opened with a cyclohexane-1,4-diamine or a primary or secondary amine to form the corresponding semi-amides, before being reacted in the second step to the diamide by a complementary primary or secondary amine or a cyclohexane-1,4-diamine in the presence of dehydrating agents. In the second step, in particular, it may be advantageous to activate the carboxylic acid function of the intermediate semi-amide before producing the diamide by conversion into a carboxylic acid equivalent (for example acid chloride or active ester). The reactions with anhydrides preferably take place in polar or non-polar aprotic solvents such as DMF, DMSO, diethyl ether, diisopropylether, THF, toluene, dichloromethane or acetonitrile at temperatures between −20 and +110° C., preferably between −10 and +40° C.

In the case of reactions with acid chlorides, polar or non-polar aprotic solvents, to which an organic or inorganic auxiliary base, preferably tertiary amines such as triethylamine, diisopropylethylamine or DMAP, has been added, are also used. In addition to amines of this type, pyridine, for example, is also suitable as a base and as a solvent. Preferably acid chlorides are reacted with amines at −10 and +40° C. in dichloromethane or chloroform in the presence of triethylamine or pyridine and optionally catalytic amounts of DMAP. For the reaction of the carboxylic acid function of an intermediate semi-amide with a further amine, the entire range of methods for producing amides known to a person skilled in the art is available. Organic or inorganic dehydrating agents such as a molecular sieve, magnesium sulphate, sulphuric acid or carbodiimides such as DCC or DIC, the latter optionally in the presence of HOBt (1-hydroxybenzotriazole), are advantageously used. These reactions are also preferably conducted in polar or non-polar aprotic solvents at temperatures between −20 and +110° C., preferably between −10 and +40° C. The protecting groups are optionally then cleaved.

EXAMPLES

Certain embodiments of the present invention may be further understood by reference to the following specific examples. These examples and the terminology used herein are for the purpose of describing particular embodiments only and are not intended to be limiting.

The yields of compounds produced have not been optimised.

All temperatures are uncorrected.

The term “ether” denotes diethyl ether, “EE” ethyl acetate and “DCM” dichloromethane. The term “equivalent” denotes amount of substance equivalent, “mp.” melting point or melting range, “decomp.” decomposition, “RT” room temperature, “abs.” absolute (anhydrous), “rac.” racemic, “conc.” concentrated, “min” minutes, “h” hours, “d” days, “vol. %” volume percent, “m %” mass percent and “M” is a concentration in mol/l.

Silica gel 60 (0.040-0.063 mm) from E. Merck, Darmstadt was used as the stationary phase for column chromatography.

Thin-layer chromatography tests were carried out using HPTLC chromatoplates, silica gel 60 F 254, from E. Merck, Darmstadt.

The mixing ratios of eluants for chromatographic tests are always given in volume/volume.

The compounds used in the following were either commercially available, or production thereof is known from the prior art or has been derived from the prior art in a manner obvious to a person skilled in the art.

General Directions:

0.1 mmol cyclohexane-1,4-diamine and 0.1 mmol diisopropylethylamine in THF were added dropwise to 0.1 mmol of the anhydride. The mixture was stirred for 12 h and 2 M HCl were then added to the reaction solution. The carboxylic acid derivative was obtained by extraction with 3×2 ml dichloromethane and removal of the solvent.

0.1 mmol of the corresponding amine (see Table 1) and 1 equivalent dilsopropylcarbodiimide and 1 equivalent 1-hydroxybenzotriazole were added to the resultant product. The mixture was stirred for 12 h and a 1 M sodium carbonate solution was then added. The product was obtained by extraction with 3×2 ml ethyl acetate/THF in each case and removal of the solvent.

Table 1 cites the carboxylic acids used for the last step for the examples.

TABLE 1 List of examples and diagrams of the amine used in the last synthesis step. Example Name of example compound 1

N-[1-(2,6-dichloro-benzyl)-pyrrolidin-3-yl]- N′-[4-dimethylamino-4-(4-methyl-benzyl)- cyclohexyl]-succinamide 2

N-[4-(3-chloro-benzyl)-4-dimethylamino- cyclohexyl]-N′-(2-oxo-tetrahydro-furan-3- yl)-succinamide 3

N-[4-(4-chloro-benzyl)-4-dimethylamino- cyclohexyl]-N′-(3,3-diphenyl-propyl)- succinamide 4

N-[4-dimethylamino-4-(4-methyl-benzyl)- cyclohexyl]-4-[4-(7-methoxy- benzo[1,3]dioxol-5-ylmethyl)-piperazin-1- yl]-4-oxo-butyramide 5

N-[4-(4-chloro-benzyl)-4-dimethylamino- cyclohexyl]-4-(3,6-dihydro-2H-pyridin-1- yl)-4-oxo-butyramide 6

N-[4-dimethylamino-4-(4-methyl-benzyl)- cyclohexyl]-4-oxo-4-(4-m-tolyl-piperazin-1- yl)-butyramide 7

2-{3-[4-(4-chloro-benzyl)-4-dimethylamino- cyclohexylcarbamoyl]-propionylamino}- propanoic acid ethylester 8

N-[4-(3-chloro-benzyl)-4-dimethylamino- cyclohexyl]-4-(8-fluoro-1,3,4,5-tetrahydro- pyrido[4,3-b]indol-2-yl)-4-oxo-butyramide 9

3-{3-[4-dimethylamino-4-(4-methyl-benzyl)- cyclohexylcarbamoyl]-propionylamino}- propanoic acid ethylester 10

N-[4-dimethylamino-4-(4-methyl-benzyl)- cyclohexyl]-4-[4-(5-methyl-pyrazin-2- carbonyl)-piperazin-1-yl]-4-oxo-butyramide 11

N-[4-dimethylamino-4-(4-methyl-benzyl)- cyclohexyl]-N′-methyl-N′-[2-(2,2,2-trifluoro- acetylamino)-ethyl]-succinamide 12

N-[4-(3-chloro-benzyl)-4-dimethylamino- cyclohexyl]-N′-(2-pyridin-2-yl-ethyl)- succinamide 13

N-[4-(4-chloro-benzyl)-4-dimethylamino- cyclohexyl]-4-oxo-4-thiomorpholin-4-yl- butyramide 14

N-[4-(4-chloro-benzyl)-4-dimethylamino- cyclohexyl]-4-[4-(5-methyl-pyrazin-2- carbonyl)-piperazin-1-yl]-4-oxo-butyramide 15

N-[4-dimethylamino-4-(3-methyl-benzyl)- cyclohexyl]-N′-(2-thiophen-2-yl-ethyl)- succinamide 16

N-[4-(4-chloro-benzyl)-4-dimethylamino- cyclohexyl]-4-[4-(4-ethoxy-phenyl)- piperazin-1-yl]-4-oxo-butyramide 17

N-allyl-N′-[4-(4-chloro-benzyl)-4- dimethylamino-cyclohexyl]-N-methyl- succinamide 18

5-[4-(2,5-dimethoxy-benzyl)-piperazin-1- yl]-5-oxo-valeric acid (4-benzyl-4- dimethylamino-cyclohexyl)-amide 19

4-(3,6-dihydro-2H-pyridin-1-yl)-N-[4- dimethylamino-4-(4-methyl-benzyl)- cyclohexyl]-4-oxo-butyramide 20

N-[4-dimethylamino-4-(3-methyl-benzyl)- cyclohexyl]-4-(4-methyl-piperidin-1-yl)-4- oxo-butyramide 21

N-[4-dimethylamino-4-(4-methyl-benzyl)- cyclohexyl]-4-oxo-4-(4-pyridin-2-yl- piperazin-1-yl)-butyramide 22

({3-[4-dimethylainino-4-(3-methyl-benzyl)- cyclohexylcarbamoyl]-propionyl}-methyl- amino)-acetic acid benzyl ester 23

4-[4-(2,6-dichloro-benzyl)-piperazin-1-yl]- N-[4-dimethylamino-4-(3-methyl-benzyl)- cyclohexyl]-4-oxo-butyramide 24

{[4-(4-benzyl-4-dimethylamino- cyclohexylcarbamoyl)-butyryl]-methyl- amino}-acetic acid tert butyl ester 25

5-[4-(2-fluoro-5-methoxy-benzyl)-piperazin- 1-yl]-5-oxo-valeric acid (4-benzyl-4- dimethylamino-cyclohexyl)-amide 26

N-[4-(4-chloro-benzyl)-4-dimethylamino- cyclohexyl]-N′-(3-methoxy-propyl)- succinamide 27

4-[4-(4-Acetyl-phenyl)-piperazin-1-yl]-N-[4- dimethylamino-4-(4-methyl-benzyl)- cyclohexyl]-4-oxo-butyramide 28

4-{3-[4-dimethylamino-4-(4-methyl-benzyl)- cyclohexylcarbamoyl]-propionyl}-piperazin- 1-carboxylic acid-tert-butylester 29

N-[4-(3-chloro-benzyl)-4-dimethylamino- cyclohexyl]-N′-(tetrahydro-furan-2- ylmethyl)-succinamide 30

2-{3-[4-(3-chloro-benzyl)-4-dimethylamino- cyclohexylcarbamoyl]-propionylamino}- propanoic acid ethylester 31

N-(3-bromo-benzyl)-N′-[4-dimethylamino-4- (3-methyl-benzyl)-cyclohexyl]-succinamide 32

3-(4-chloro-phenyl)-2-{3-[4-dimethylamino- 4-(4-methyl-benzyl)-cyclohexylcarbamoyl]- propionylamino}-propanoic acid methylester 33

N-[4-(3-chloro-benzyl)-4-dimethylamino- cyclohexyl]-4-[4-(5-methyl-pyrazin-2- carbonyl)-piperazin-1-yl]-4-oxo-butyramide 34

N-[4-(4-chloro-benzyl)-4-dimethylamino- cyclohexyl]-N′-naphthalen-1-ylmethyl- succinamide 35

N-[4-dimethylamino-4-(3-methyl-benzyl)- cyclohexyl]-4-[4-(3-fluoro-4-methoxy- benzyl)-piperazin-1-yl]-4-oxo-butyramide 36

N-[4-dimethylamino-4-(4-methyl- benzyl)-cyclohexyl]-N′-[2-(1H-indol-3- yl)-ethyl]-N′-methyl-succinamide 37

(4-{3-[4-(3-chloro-benzyl)-4- dimethylamino-cyclohexylcarbamoyl]- propionylamino}-benzyl)-phosphonic acid diethylester 38

N-[4-dimethylamino-4-(4-methyl-benzyl)- cyclohexyl]-N′-methyl-N′-(2-pyridin-2-yl- ethyl)-succinamide 39

N-[4-(3-chloro-benzyl)-4-dimethylamino- cyclohexyl]-4-(3,6-dihydro-2H-pyridin-1- yl)-4-oxo-butyramide 40

N-[4-dimethylamino-4-(3-methyl-benzyl)- cyclohexyl]-N′-(1-methyl-3-phenyl-propyl)- succinamide 41

5-[4-(5-methyl-pyrazin-2-carbonyl)- piperazin-1-yl]-5-oxo-valeric acid (4-benzyl- 4-dimethylamino-cyclohexyl)-amide 42

N-[4-(3-chloro-benzyl)-4-dimethylamino- cyclohexyl]-N′-(2-chloro-6-methyl-benzyl)- succinamide 43

N-allyl-N′-[4-(3-chloro-benzyl)-4- dimethylamino-cyclohexyl]-N-methyl- succinamide 44

N-[4-(4-chloro-benzyl)-4-dimethylamino- cyclohexyl]-Nt-cyclopentyl-succinamide 45

N-[4-dimethylamino-4-(4-methyl-benzyl)- cyclohexyl]-N′-(tetrahydro-furan-2- ylmethyl)-succinamide 46

(4-{3-[4-dimethylamino-4-(3-methyl- benzyl)-cyclohexylcarbamoyl]- propionylamino}-benzyl)-phosphonic acid diethylester 47

N-[4-(4-chloro-benzyl)-4-dimethylamino- cyclohexyl]-4-[4-(2-methoxy-phenyl)- piperazin-1-yl]-4-oxo-butyramide 48

N-[4-dimethylamino-4-(3-methyl-benzyl)- cyclohexyl]-4-[4-(3-methoxy-phenyl)- piperazin-1-yl]-4-oxo-butyramide 49

N-[4-(4-chloro-benzyl)-4-dimethylamino- cyclohexyl]-N′-(3,5-difluoro-benzyl)- succinamide 50

N-[4-(4-chloro-benzyl)-4-dimethylamino- cyclohexyl]-N′-(2-methyl-benzyl)- succinamide 51

N-[4-dimethylamino-4-(4-methyl-benzyl)- cyclohexyl]-4-oxo-4-{4-[(2,2,2-trifluoro- acetylamino)-methyl]-piperidin-1-yl}- butyramide 52

N-[4-(4-chloro-benzyl)-4-dimethylamino- cyclohexyl]-N′-[2-(1H-indol-3-yl)-ethyl]- succinamide 53

N-[4-(3-chloro-benzyl)-4-dimethylamino- cyclohexyl]-N′-[2-(1H-indol-3-yl)-ethyl]-N′- methyl-succinamide 54

5-[4-(7-methoxy-benzo[1,3]dioxol-5- ylmethyl)-piperazin-1-yl]-5-oxo-valeric acid (4-benzyl-4-dimethylamino-cyclohex)/1)- amide 55

N-benzyl-N′-[4-dimethylamino-4-(3-methyl- benzyl)-cyclohexyl]-N-(2-hydroxy-ethyl)- succinamide 56

5-[4-(2,3-dimethyl-phenyl)-piperazin-1-yl]- 5-oxo-valeric acid (4-benzyl-4- dimethylamino-cyclohexyl)-amide 57

N-[4-(4-chloro-benzyl)-4-dimethylamino- cyclohexyl]-N′-[2-(1H-indol-3-yl)-ethyl]-N′- methyl-succinamide 58

N-[4-dimethylamino-4-(4-methyl-benzyl)- cyclohexyl]-4-[4-(2,3-dimethyl-phenyl)- piperazin-1- yl]-4-oxo-butyramide 59

Glutaric acid-(4-benzyl-4-dimethylamino- cyclohexyl)-amide (1,2,3,4-tetrahydro- naphthalen-1-yl)-amide 60

N-[4-(4-chloro-benzyl)-4-dimethylamino- cyclohexyl]-4-(4-methyl-piperidin-1-yl)-4- oxobutyramide 61

2-{3-[4-dimethylamino-4-(4-methyl-benzyl)- cyclohexylcarbamoyl]-propionylamino}- propanoic acid-tert-butylester 62

5-(4-cycloheptyl-piperazin-1-yl)-5-oxo- valeric acid (4-benzyl-4-dimethylamino- cyclohexyl)-amide 63

Glutaric acid-(4-benzyl-4-dimethylamino- cyclohexyl)-amide[2-(4-fluoro-phenyl)- ethyl]-amide 64

Glutaric acid-(4-benzyl-4-dimethylamino- cyclohexyl)-amide[1-(2,6-dichloro-benzyl)- pyrrolidin-3-yl]-amide 65

N-[4-(4-chloro-benzyl)-4-dimethylamino- cyclohexyl]-4-(1,4-dioxa-8-aza- spiro[4.5]dec-8-yl)-4-oxo-butyramide 66

N-[4-(3-chloro-benzyl)-4-dimethylamino- cyclohexyl]-4-oxo-4-thiomorpholin-4-yl- butyramide 67

4-(4-benzoyl-piperidin-1-yl)-N-[4- dimethylamino-4-(3-methyl-benzyl)- cyclohexyl]-4-oxo-butyramide 68

N-[4-(4-chloro-benzyl)-4-dimethylamino- cyclohexyl]-N′-(2,4-dimethoxy-benzyl)- succinamide 69

N-[4-dimethylamino-4-(3-methyl-benzyl)- cyclohexyl]-N′-(1,2,3,4-tetrahydro- naphthalen-1-yl)-succinamide 70

N-[4-(4-chloro-benzyl)-4-dimethylamino- cyclohexyl]-N′-ethyl-N′-pyridin-4-ylmethyl- succinamide 71

N-[2-(3,4-dimethoxy-phenyl)-ethyl]-N′-[4- dimethylamino-4-(3-methyl-benzyl)- cyclohexyl]-N-methyl-succinamide 72

N-[4-(4-chloro-benzyl)-4-dimethylamino- cyclohexyl]-N′-methyl-N′-pyridin-3- ylmethyl-succinamide 73

N-[4-(3-chloro-benzyl)-4-dimethylamino- cyclohexyl]-N′-pyridin-2-ylmethyl- succinamide 74

N-[4-(3-chloro-benzyl)-4-dimethylamino- cyclohexyl]-N′-(2-methyl-benzyl)- succinamide 75

N-[4-dimethylamino-4-(3-methyl-benzyl)- cyclohexyl]-N′-(4-methoxy-phenyl)- succinamide 76

N-[4-dimethylamino-4-(3-methyl-benzyl)- cyclohexyl]-N′-indan-2-yl-succinamide 77

N-[4-(3-chloro-benzyl)-4-dimethylamino- cyclohexyl]-N′-(1-methyl-3-phenyl-propyl)- succinamide 78

N-(2-chloro-6-methyl-benzyl)-N′-[4- dimethylamino-4-(3-methyl-benzyl)- cyclohexyl]-succinamide 79

N-[4-dimethylamino-4-(4-methyl-benzyl)- cyclohexyl]-4-[4-(4-methoxy-phenyl)- piperazin-1-yl]-4-oxo-butyramide 80

N-[4-dimethylamino-4-(4-methyl-benzyl)- cyclohexyl]-N′-[2-(4-fluoro-phenyl)-ethyl]- succinamide 81

Glutaric acid-(4-benzyl-4-dimethylamino- cyclohexyl)-amide 4-dimethylamino- benzylamide 82

N-[4-(3-chloro-benzyl)-4-dimethylamino- cyclohexyl]-N′-(3,5-dichloro-benzyl)- succinamide 83

N-[4-(4-chloro-benzyl)-4-dimethylamino- cyclohexyl]-N′-(1-methyl-3-phenyl-propyl)- succinamide 84

4-{3-[4-(3-chloro-benzyl)-4-dimethylamino- cyclohexylcarbamoyl]-propionyl}-piperazin- 1-carboxylic acid ethylester 85

N-[4-dimethylamino-4-(3-methyl-benzyl)- cyclohexyl]-N′-(4-methoxy-benzyl)- succinamide 86

N-[4-(4-chloro-benzyl)-4-dimethylamino- cyclohexyl]-4-(2,6-dimethyl-morpholin-4- yl)-4-oxo-butyramide 87

N-[4-dimethylamino-4-(4-methyl-benzyl)- cyclohexyl]-4-oxo-4-(4-phenyl-3,6-dihydro- 2H-pyridin-1-yl)-butyramide 88

N-[4-(4-chloro-benzyl)-4-dimethylamino- cyclohexyl]-N′-[2-(3-fluoro-phenyl)-ethyl]- succinamide 89

4-[4-(4-allyloxy-benzyl)-piperazin-1-yl]-N- [4-dimethylamino-4-(3-methyl-benzyl)- cyclohexyl]-4-oxo-butyramide 90

Glutaric acid-(4-benzyl-4-dimethylamino- cyclohexyl)-amide[2-(5-bromo-2-methoxy- phenyl)-ethyl]-amide 91

5-[4-(3-methoxy-phenyl)-piperazin-1-yl]-5- oxo-valeric acid (4-benzyl-4-dimethylamino- cyclohexyl)-amide 92

N-[4-(3-chloro-benzyl)-4-dimethylamino- cyclohexyl]-4-(4-methyl-piperidin-1-yl)-4- oxo-butyramide 93

(4-{3-[4-(4-chloro-benzyl)-4- dimethylamino-cyclohexylcarbamoyl]- propionylamino}-benzyl)-phosphonic acid diethylester 94

N-[4-dimethylamino-4-(4-methyl-benzyl)- cyclohexyl]-4-oxo-4-(4-o-tolyl-piperazin-1- yl)-butyramide 95

N-[4-dimethylamino-4-(3-methyl-benzyl)- cyclohexyl]-N′-[2-(3-fluoro-phenyl)-ethyl]- succinamide 96

4-[4-(4-chloro-phenyl)-piperazin-1-yl]-N-[4- dimethylamino-4-(4-methyl-benzyl)- cyclohexyl]-4-oxo-butyramide 97

N-[4-(3-chloro-benzyl)-4-dimethylamino- cyclohexyl]-N′-[1-(4-fluoro-phenyl)-ethyl]- succinamide 98

N-[4-(4-chloro-benzyl)-4-dimethylamino- cyclohexyl]-N′-[1-(4-trifluoromethyl- benzyl)-pyrrolidin-3-yl]-succinamide 99

N-[4-(3-chloro-benzyl)-4-dimethylamino- cyclohexyl]-N′-[2-(1H-indol-3-yl)-ethyl]- succinamicle 100

N-[4-(4-chloro-benzyl)-4-dimethylamino- cyclohexyl]-N′-indan-5-yl-succinamide 101

N-(4-benzyloxy-phenyl)-N′-[4- dimethylamino-4-(4-methyl-benzyl)- cyclohexyl]-succinamide 102

2-{3-[4-dimethylamino-4-(3-methyl-benzyl)- cyclohexylcarbamoyl]-propionylamino}-3- methyl-valeric acid tert-butyl ester 103

4-(4-benzyl-piperidin-1-yl)-N-[4- dimethylamino-4-(3-methyl-benzyl)- cyclohexyl]-4-oxo-butyramide 104

N-[4-(4-chloro-benzyl)-4-dimethylamino- cyclohexyl]-4-[4-(4-fluoro-phenyl)-3,6- dihydro-2H-pyridin-1-yl]-4-oxo-butyramide 105

N-[4-dimethylamino-4-(4-methyl-benzyl)- cyclohexyl]-N′-(1,2-dimethyl-propyl)- succinamide 106

N-[4-dimethylamino-4-(3-methyl-benzyl)- cyclohexyl]-4-(8-fluoro-1,3,4,5-tetrahydro- pyrido[4,3-b]indol-2-yl)-4-oxo-butyramide 107

4-[4-(3-chloro-benzoyl)-piperazin-1-yl]-N- [4-dimethylamino-4-(3-methyl-benzyl)- cyclohexyl]-4-oxo-butyramide 108

N-[4-(4-chloro-benzyl)-4-dimethylamino- cyclohexyl]-N′-(4-methoxy-phenyl)- succinamide 110

5-[4-(2,6-dichloro-benzyl)-piperazin-1-yl]-5- oxo-valeric acid (4-benzyl-4-dimethylamino- cyclohexyl)-amide 111

N-[4-dimethylamino-4-(3-methyl-benzyl)- cyclohexyl]-N′-[2-(1H-indol-3-yl)-ethyl]-N′- methyl-succinamide 112

N-[4-dimethylamino-4-(3-methyl-benzyl)- cyclohexyl]-N′-[1-(4-fluoro-phenyl)-ethyl]- succinamide 113

4-[4-(4-chloro-phenyl)-piperazin-1-yl]-N-[4- dimethylamino-4-(3-methyl-benzyl)- cyclohexyl]-4-oxo-butyramide 114

N-[4-(3-chloro-benzyl)-4-dimethylamino- cyclohexyl]-4-oxo-4-(4-oxo-1-phenyl-1,3,8- triaza-spiro[4.5]dec-8-yl)-butyramide 115

N-benzyl-N′-[4-dimethylamino-4-(3-methyl- benzyl)-cyclohexyl]-N-methyl-succinamide 116

N-[4-(3-chloro-benzyl)-4-dimethylamino- cyclohexyl]-N′-(3,5-difluoro-benzyl)- succinamide 117

N-[4-dimethylamino-4-(3-methyl-benzyl)- cyclohexyl]-N′-[2-(4-fluoro-phenyl)-ethyl]- succinamide 118

N-[4-dimethylamino-4-(3-methyl-benzyl)- cyclohexyl]-N′-[2-(1H-indol-3-yl)-ethyl]- succinamide 119

N-(2-benzylsulphanyl-ethyl)-N′-[4- dimethylamino-4-(3-methyl-benzyl)- cyclohexyl]-succinamide 120

N-[4-(3-chloro-benzyl)-4-dimethylamino- cyclohexyl]-N′-(2,4-difluoro-benzyl)- succinamide 121

N-[4-(3-chloro-benzyl)-4-dimethylamino- cyclohexyl]-N′-phenethyl-succinamide 122

N-[4-dimethylamino-4-(3-methyl-benzyl)- cyclohexyl]-N′-(1-naphthalen-2-yl-ethyl)- succinamide 123

N-[4-(3-chloro-benzyl)-4-dimethylamino- cyclohexyl]-N′-(1-methoxymethyl-2-phenyl- ethyl)-succinamide 124

N-[4-(3-chloro-benzyl)-4-dimethylamino- cyclohexyl]-N′-(3,4-dichloro-benzyl)- succinamide 125

N-[4-(3-chloro-benzyl)-4-dimethylamino- cyclohexyl]-N′-furan-2-ylmethyl- succinamide 126

N-[4-dimethylamino-4-(4-methyl-benzyl)- cyclohexyl]-N′-(1,2,3,4-tetrahydro- naphthalen-1-yl)-succinamide 127

N-[4-(3-chloro-benzyl)-4-dimethylamino- cyclohexyl]-N′-(4-fluoro-benzyl)- succinamide 128

N-[4-dimethylamino-4-(3-methyl-benzyl)- cyclohexyl]-N′-indan-1-yl-succinamide 129

N-[4-(3-chloro-benzyl)-4-dimethylamino- cyclohexyl]-4-(3,5-dimethyl-piperidin-1-yl)- 4-oxo-butyramide 130

N-[4-dimethylamino-4-(3-methyl-benzyl)- cyclohexyl]-N′-phenethyl-succinamide 131

N-[4-dimethylamino-4-(4-methyl-benzyl)- cyclohexyl]-N′-phenethyl-succinamide 132

N-(2-benzylsulphanyl-ethyl)-N′-[4-(3- chloro-benzyl)-4-dimethylamino- cyclohexyl]-succinamide 133

N-[4-(3-chloro-benzyl)-4-dimethylamino- cyclohexyl]-N′-(2,5-dichloro-benzyl)- succinamide 134

4-[4-(3-chloro-benzoyl)-piperazin-1-yl]-N- [4-(4-chloro-benzyl)-4-dimethylamino- cyclohexyl]-4-oxo-butyramide 135

N-[4-(4-chloro-benzyl)-4-dimethylamino- cyclohexyl]-N′-(1-phenyl-propyl)- succinamide 136

N-(4-bromo-2-fluoro-benzyl)-N′-[4- dimethylamino-4-(3-methyl-benzyl)- cyclohexyl]-succinamide 137

N-[4-(3-chloro-benzyl)-4-dimethylamino- cyclohexyl]-N′-methyl- N′-pyridin-3-ylmethyl- succinamide 138

N-[4-dimethylamino-4-(4-methyl-benzyl)- cyclohexyl]-N′-(2-ethoxy-benzyl)- succinamide 139

N-[4-dimethylamino-4-(3-methyl-benzyl)- cyclohexyl]-N′-(2-(5-methoxy-1H-indol-3- yl)-ethyl]-succinamide 140

N-(4-sec-butyl-phenyl)-N′-[4-(4-chloro- benzyl)-4-dimethylamino-cyclohexyl]- succinamide 141

5-oxo-5-(4-phenyl-3,6-dihydro-2H-pyridin- 1-yl)-valeric acid (4-benzyl-4- dimethylamino-cyclohexyl)-amide 142

5-oxo-5-(4-phenyl-3,6-dihydro-2H-pyridin- 1-yl)-valeric acid (4-benzyl-4- dimethylamino-cyclohexyl)-amide 143

N-[4-(3-chloro-benzyl)-4-dimethylamino- cyclohexyl]-N′-[2-(3-fluoro-phenyl)-ethyl]- succinamide 144

N-(3-bromo-benzyl)-N′-[4-(3-chloro- benzyl)-4-dimethylamino-cyclohexyl]- succinamide 145

N-(4-bromo-2-fluoro-benzyl)-N′-[4-(3- chloro-benzyl)-4-dimethylamino- cyclohexyl]-succinamide 146

N-[4-(3-chloro-benzyl)-4-dimethylamino- cyclohexyl]-N′-(1-phenyl-propyl)- succinamide 147

N-[4-dimethylamino-4-(3-methyl-benzyl)- cyclohexyl]-N′-(4-fluoro-2-trifluoromethyl- benzyl)-succinamide 148

N-[4-(3-chloro-benzyl)-4-dimethylamino- cyclohexyl]-N′-indan-2-yl-succinamide 149

N-[4-dimethylamino-4-(3-methyl-benzyl)- cyclohexyl]-4-oxo-4-(4-phenyl-3,6-dihydro- 2H-pyridin-1-yl)-butyramide 150

N-[4-(4-chloro-benzyl)-4-dimethylamino- cyclohexyl]-N′-[2-(2-fluoro-phenyl)-ethyl]- succinamide 151

N-[4-dimethylamino-4-(4-methyl-benzyl)- cyclohexyl]-N′-[2-(2-fluoro-phenyl)-ethyl]- succinamide 152

Glutaric acid-(4-benzyl-4-dimethylamino- cyclohexyl)-amide[2-(2-fluoro-phenyl)- ethyl]-amide 153

N-[2-(2-chloro-phenyl)-ethyl]-N′-[4- dimethylamino-4-(4-methyl-benzyl)- cyclohexyl]-succinamide 154

N-[4-(3-chloro-benzyl)-4-dimethylamino- cyclohexyl]-N′-(3,4-difluoro-benzyl)- succinamide 155

N-benzyl-N-(2-cyano-ethyl)-N′-[4- dimethylamino-4-(4-methyl-benzyl)- cyclohexyl]-succinamide 156

N-[4-(3-chloro-benzyl)-4-dimethylamino- cyclohexyl]-N′-(3-methyl-benzyl)- succinamide 157

N-[4-(3-chloro-benzyl)-4-dimethylamino- cyclohexyl]-N′-(4-fluoro-3-trifluoromethyl- benzyl)-succinamide 159

N-[4-(3-chloro-benzyl)-4-dimethylamino- cyclohexyl]-N′-[2-(2-chloro-phenyl)-ethyl]- succinamide 160

N-[4-(3-chloro-benzyl)-4-dimethylamino- cyclohexyl]-N′-[2-(4-chloro-phenyl)-ethyl]- succinamide 161

N-[4-(3-chloro-benzyl)-4-dimethylamino- cyclohexyl]-N′-[2-(2,4-dichloro-phenyl)- ethyl]-succinamide 162

N-[4-(3-chloro-benzyl)-4-dimethylamino- cyclohexyl]-N′-indan-1-yl-succinamide 163

N-[4-(4-chloro-benzyl)-4-dimethylamino- cyclohexyl]-N′-indan-1-yl-succinamide 164

N-[2-(4-chloro-phenyl)-propyl]-N′-[4- dimethylamino-4-(3-methyl-benzyl)- cyclohexyl]-succinamide 165

N-(3-bromo-benzyl)-N′-[4-(4-chloro- benzyl)-4-dimethylamino-cyclohexyl]- succinamide 167

N-[4-(3-chloro-benzyl)-4-dimethylamino- cyclohexyl]-N′-(3-phenyl-propyl)- succinamide 168

N-[4-dimethylamino-4-(4-methyl-benzyl)- cyclohexyl]-N′-(2-p-tolyl-ethyl)-succinamide 169

N-[4-(3-chloro-benzyl)-4-dimethylamino- cyclohexyl]-N′-(2-thiophen-2-yl-ethyl)- succinamide 170

Glutaric acid-(4-benzyl-4-dimethylamino- cyclohexyl)-amide[2-(4-chloro-phenyl)- propyl]-amide 171

N-benzyl-N′-[4-(3-chloro-benzyl)-4- dimethylamino-cyclohexyl]-N-methyl- succinamide 172

N-[4-(3-chloro-benzyl)-4-dimethylamino- cyclohexyl]-N′-[2-(3-chloro-phenyl)-ethyl]- succinamide 173

Glutaric acid-(4-benzyl-4-dimethylamino- cyclohexyl)-amide[2-(2-ethoxy-phenyl)- ethyl]-amide 174

Glutaric acid-(4-benzyl-4-dimethylamino- cyclohexyl)-amide phenethyl-amide 175

Glutaric acid-(4-benzyl-4-dimethylamino- cyclohexyl)-amide[2-(3-chloro-phenyl)- ethyl]-amide 176

N-[4-(3-chloro-benzyl)-4-dimethylamino- cyclohexyl]-N′-[1-(3-methoxy-phenyl)- ethyl]-succinamide 177

Glutaric acid-(4-benzyl-4-dimethylamino- cyclohexyl)-amide (1,3-dimethyl-butyl)- amide 178

N-benzyl-N′-[4-dimethylamino-4-(3-methyl- benzyl)-cyclohexyl]-N-ethyl-succinamide 179

N-(4-chloro-benzyl)-N′-[4-(3-chloro- benzyl)-4-dimethylamino-cyclohexyl]- succinamide 180

N-[4-(3-chloro-benzyl)-4-dimethylamino- cyclohexyl]-N′-[2-(2-fluoro-phenyl)-ethyl]- succinamide 181

N-[4-dimethylamino-4-(3-methyl-benzyl)- cyclohexyl]-N′-(2-fluoro-benzyl)- succinamide 182

N-[2-(4-chloro-phenyl)-ethyll-N′-[4- dimethylamino-4-(3-methyl-benzyl)- cyclohexyl]-succinamide 183

N-[2-(2-chloro-phenyl)-ethyl]-N′-[4- dimethylamino-4-(3-methyl-benzyl)- cyclohexyl]-succinamide 184

N-[2-(3-chloro-phenyl)-ethyl]-N′-[4- dimethylamino-4-(3-methyl-benzyl)- cyclohexyl]-succinamide 185

N-benzyl-N′-[4-(3-chloro-benzyl)-4- dimethylamino-cyclohexyl]-N-(2-cyano- ethyl)-succinamide 186

N-[4-(3-chloro-benzyl)-4-dimethylamino- cyclohexyl]-N′-(3-chloro-4-fluoro-benzyl)- succinamide 187

N-[4-dimethylamino-4-(3-methyl-benzyl)- cyclohexyl]-N′-(2-trifluoromethyl-benzyl)- succinamide 188

N-[2-(2,4-dichloro-phenyl)-ethyl]-N′-[4- dimethylamino-4-(3-methyl-benzyl)- cyclohexyl]-succinamide 189

N-benzyl-N′-[4-(3-chloro-benzyl)-4- dimethylamino-cyclohexyl]-N-ethyl- succinamide 190

N-[2-(4-chloro-phenyl)-ethyl]-N′-[4- dimethylamino-4-(4-methyl-benzyl)- cyclohexyl]-succinamide 191

5-oxo-5-(4-o-tolyl-piperazin-1-yl)-valeric acid (4-benzyl-4-dimethylamino- cyclohexyl)-amide 192

N-[4-(3-chloro-benzyl)-4-dimethylamino- cyclohexyl]-N′-[3-(methyl-phenyl-amino)- propyl]-succinamide 193

N-[4-(3-chloro-benzyl)-4-dimethylamino- cyclohexyl]-4-[4-(5-chloro-2-methyl- phenyl)-piperazin-1-yl]-4-oxo-butyramide 194

N-[4-dimethylamino-4-(3-methyl-benzyl)- cyclohexyl]-N′-[2-(2-ethoxy-phenyl)-ethyl]- succinamide 195

4-[4-(4-chloro-benzoyl)-piperidin-1-yl]-N- [4-(3-chloro-benzyl)-4-dimethylamino- cyclohexyl]-4-oxo-butyramide 196

N-[4-(3-chloro-benzyl)-4-dimethylamino- cyclohexyl]-N′-[2-(2-ethoxy-phenyl)-ethyl]- succinamide 197

N-[2-(2,6-dichloro-phenyl)-ethyl]-N′-[4- dimethylamino-4-(3-methyl-benzyl)- cyclohexyl]-succinamide 198

N-benzhydryl-N′-[4-(3-chloro-benzyl)-4- dimethylamino-cyclohexyl]-succinamide 199

N-[4-(3-chloro-benzyl)-4-dimethylamino- cyclohexyl]-N′-cyclooctyl-succinamide 200

N-[4-(3-chloro-benzyl)-4-dimethylamino- cyclohexyl]-N′-[2-(4-phenoxy-phenyl)- ethyl]-succinamide 201

N-[4-dimethylamino-4-(3-methyl-benzyl)- cyclohexyl]-N′-(2,3-dimethyl-benzyl)- succinamide 202

4-[4-(5-chloro-2-methyl-phenyl)-piperazin- 1-yl]-N-[4-dimethylamino-4-(3-methyl- benzyl)-cyclohexyl]-4-oxo-butyramide 203

4-[4-(4-chloro-benzoyl)-piperidin-1-yl]-N- [4-dimethylamino-4-(3-methyl-benzyl)- cyclohexyl]-4-oxo-butyramide 204

N-[4-(3-chloro-benzyl)-4-dimethylamino- cyclohexyl]-N′-(1,2,3,4-tetrahydro- naphthalen-1-yl)-succinamide 205

N-(2-chloro-benzyl)-N′-[4-dimethylamino-4- (3-methyl-benzyl)-cyclohexyl]-succinamide 206

N-(2-chloro-benzyl)-N′-[4-(3-chloro- benzyl)-4-dimethylamino-cyclohexyl]- succinamide 207

N-[4-(3-chloro-benzyl)-4-dimethylamino- cyclohexyl]-N′-(3-fluoro-5-trifluoromethyl- benzyl)-succinamide 208

N-[4-(3-chloro-benzyl)-4-dimethylamino- cyclohexyl]-N′-(1-p-tolyl-ethyl)-succinamide 209

N-[2-(2,6-dichloro-benzylsulphanyl)-ethyl]- N′-[4-dimethylamino-4-(4-methyl-benzyl)- cyclohexyl]-succinamide 210

N-[4-(3-chloro-benzyl)-4-dimethylamino- cyclohexyl]-N′-[2-(2,6-dichloro- benzylsulphanyl)-ethyl]-succinamide 211

N-[4-(3-chloro-benzyl)-4-dimethylamino- cyclohexyl]-N′-[2-(3-trifluoromethyl- phenyl)-ethyl]-succinamide 212

N-[2-(3,4-dichloro-phenyl)-ethyl]-N′-[4- dimethylamino-4-(3-methyl-benzyl)- cyclohexyl]-succinamide 213

N-[4-(3-chloro-benzyl)-4-dimethylamino- cyclohexyl]-4-[4-(2-fluoro-phenyl)- piperazin-1-yl]-4-oxo-butyramide 214

5-[4-(2,4-dimethoxy-phenyl)-piperazin-1- yl]-5-oxo-valeric acid (4-benzyl-4- dimethylamino-cyclohexyl)-amide 215

N-[4-(3-chloro-benzyl)-4-dimethylamino- cyclohexyl]-N′-(1-naplithalen-1-yl-ethyl)- succinamide 216

N-[4-dimethylamino-4-(3-methyl-benzyl)- cyclohexyl]-N′-(1-naplithalen-1-yl-ethyl)- succinamide 217

N-[4-(3-chloro-benzyl)-4-dimethylamino- cyclohexyl]-N′-(2-fluoro-benzyl)-N′-furan-2- ylmethyl-succinamide 218

N-[4-dimethylamino-4-(3-methyl-benzyl)- cyclohexyl]-N′-(2-fluoro-benzyl)-N′-furan-2- ylmethyl-succinamide 219

N-[4-(3-chloro-benzyl)-4-dimethylamino- cyclohexyl]-N′-(2,5-dimethoxy-benzyl)-N′- furan-2-ylmethyl-succinamide 220

N-(4-azepan-1-yl-4-benzyl-cyclohexyl)-4- (2,3-dihydro-indol-1-yl)-4-oxo-butyramide 221

4-(2, 3-dihydro-indol-1-yl)-N-[4- dimethylamino-4-(3-fluoro-phenyl)- cyclohexyl]-4-oxo-butyramide 222

N-(4-benzyl-4-morpholin-4-yl-cyclohexyl)- N′-(2-chloro-6-methyl-benzyl)-succinamide 223

N-(4-benzyl-4-morpholin-4-yl-cyclohexyl)- N′-[2-(3-methoxy-phenyl)-ethyl]- succinamide 224

N-(4-benzyl-4-morpholin-4-yl-cyclohexyl)- N′-(3-methyl-benzyl)-succinamide 225

N-(4-benzyl-4-morpholin-4-yl-cyclohexyl)- N′-(4-bromo-2-fluoro-benzyl)-succinamide 226

N-(4-benzyl-4-morpholin-4-yl-cyclohexyl)- N′-pyridin-4-ylmethyl-succinamide 227

N-(4-benzyl-4-morpholin-4-yl-cyclohexyl)- N′-indan-1-yl-succinamide 228

N-(4-benzyl-4-morpholin-4-yl-cyclohexyl)- N′-(2,4-dimethoxy-benzyl)-succinamide 229

N-(4-benzyl-4-morpholin-4-yl-cyclohexyl)- N′-thiophen-2-ylmethyl-succinamide 230

N-adamantan-1-ylmethyl-N′-(4-benzyl-4- morpholin-4-yl-cyclohexyl)-succinamide 231

N-(4-benzyl-4-morpholin-4-yl-cyclohexyl)- N′-(2,5-difluoro-benzyl)-succinamide 232

N-(4-benzyl-4-morpholin-4-yl-cyclohexyl)- N′-(4-tert-butyl-phenyl)-succinamide 233

N-(4-benzyl-4-morpholin-4-yl-cyclohexyl)- N′-(3,5-bis-trifluoromethyl-benzyl)- succinamide 234

N-(4-benzyl-4-morpholin-4-yl-cyclohexyl)- N′-[2-(2-ethoxy-phenyl)-ethyl]-succinamide 235

N-(4-benzyl-4-morpholin-4-yl-cyclohexyl)- N′-(3-methoxy-propyl)-succinamide 236

N-(4-benzyl-4-morpholin-4-yl-cyclohexyl)- N′-(2-morpholin-4-yl-ethyl)-succinamide 237

N-(4-benzyl-4-morpholin-4-yl-cyclohexyl)- N′-(2,5-dichloro-benzyl)-succinamide 238

N-(4-benzyl-4-morpholin-4-yl-cyclohexyl)- N′-[1-(2-benzyloxy-benzyl)-pyrrolidin-3-yl]- N′-methyl-succinamide 239

N-(4-benzyl-4-morpholin-4-yl-cyclohexyl)- 4-oxo-4-(2-pyrrolidin-1-ylmethyl-pyrrolidin- 1-yl)-butyramide 240

N-(4-benzyl-4-morpholin-4-yl-cyclohexyl)- 4-morpholin-4-yl-4-oxo-butyramide 241

N-(4-benzyl-4-morpholin-4-yl-cyclohexyl)- N′-(3-dimethylamino-propyl)-N′-methyl- succinamide 242

N-(4-benzyl-4-morpholin-4-yl-cyclohexyl)- N′-(2-phenyl-cyclopropyl)-succinamide 243

N-(4-benzyl-4-morpholrn-4-yl-cyclohexyl)- N′-naphthalen-1-ylmethyl-succinamide 244

N-(4-benzyl-4-morpholin-4-yl-cyclohexyl)- 4-(4-methyl-[1,4]diazepan-1-yl)-4-oxo- butyramide 245

N-(4-benzyl-4-morpholin-4-yl-cyclohexyl)- 4-(4-hydroxy-piperidin-1-yl)-4-oxo- butyramide 246

N-(4-benzyl-4-morpholin-4-yl-cyclohexyl)- N′-[2-(7-methyl-1H-indol-3-yl)-ethyl]- succinamide 247

N-(4-benzyl-4-morpholin-4-yl-cyclohexyl)- N′-[2-(5-methoxy-1H-indol-3-yl)-ethyl]- succinamide 248

N-(4-benzyl-4-morpholin-4-yl-cyclohexyl)- 4-oxo-4-(4-quinolin-2-ylmethyl-piperazin-1- yl)-butyramide 249

N-(4-dimethylamino-4-thiophen-2-yl- cyclohexyl)-4-oxo-4-[4-(5-trifluoromethyl- pyndrn-2-yl)-piperazin-1-yl]-butyramide 250

Glutaric acid-(1-adamantan-1-yl-ethyl)- amide (4-dimethylamino-4-thiophen-2-yl- cyclohexyl)-amide 251

N-[2-(2,6-dichloro-phenyl)-ethyl]-N′-(4- dimethylainino-4-thiophen-2-yl-cyclohexyl)- succinamide 252

N-(4-dimethylamino-4-thiophen-2-yl- cyclohexyl)-N′-(1-methyl-3-phenyl-propyl)- succinamide 253

N-benzyl-N′-(4-dimethylamino-4-thiophen- 2-yl-cyclohexyl)-N-ethyl-succinamide 254

N-[2-(4-bromo-phenyl)-ethyl]-N′-(4- dimethylamino-4-thiophen-2-yl-cyclohexyl)- succinamide 255

4-[4-(4-chloro-benzoyl)-piperidin-1-yl]-N- (4-dimethylamino-4-thiophen-2-yl- cyclohexyl)-4-oxo-butyramide 256

Glutaric acid-[1-(2,6-dichloro-benzyl)- pyrrolidin-3-yl]-amide (4-dimethylamino-4- thiophen-2-yl-cyclohexyl)-amide 257

Glutaric acid-(4-dimethylamino-4-thiophen- 2-yl-cyclohexyl)-amide (3-phenyl-propyl)- amide 258

N-(4-dimethylamino-4-phenyl-cyclohexyl)- N′-pentyl-succinamide 259

3-(4-chloro-phenyl)-2-[4-(4-dimethylamino- 4-thiophen-2-yl-cyclohexylcarbamoyl)- butyrylamino]-propanoic acid ethylester 260

Glutaric acid-(4-dimethylamino-4-thiophen- 2-yl-cyclohexyl)-amide indan-1-ylamide 261

N-adamantan-1-ylmethyl-N′-(4- dimethylamino-4-thiophen-2-yl-cyclohexyl)- succinamide 262

5-(4-benzofuran-2-ylmethyl-piperazin-1-yl)- 5-oxo-valeric acid (4-dimethylamino-4- thiophen-2-yl-cyclohexyl)-amide 263

4-[4-(4-tert-butyl-benzyl)-piperazin-1-yl]-N- (4-dimethylamino-4-phenyl-cyclohexyl)-4- oxo-butyramide 264

Glutaric acid-(4-dimethylamino-4-thiophen- 2-yl-cyclohexyl)-amide[2-(1H-indol-3-yl)- ethyl]-amide 265

N-(4-dimethylamino-4-phenyl-cyclohexyl)- 4-[4-hydroxy-4-(3-trifluoromethyl-phenyl)- piperidin-1-yl]-4-oxo-butyramide 266

5-(3,4-dihydro-1H-isoquinolin-2-yl)-5-oxo- valeric acid (4-dimethylamino-4-thiophen-2- yl-cyclohexyl)-amide 267

4-(4-benzyl-piperidin-1-yl)-N-(4- dimethylamino-4-phenyl-cyclohexyl)-4-oxo- butyramide 268

{[4-(4-dimethylamino-4-thiophen-2-yl- cyclohexylcarbamoyl)-butyryl]-methyl- amino}-acetic acid benzylester 269

N-benzyl-N′-(4-dimethylamino-4-phenyl- cyclohexyl)-N-phenethyl-succinamide 270

Glutaric acid-(4-dimethylamino-4-thiophen- 2-yl-cyclohexyl)-amide 3-trifluoromethoxy- benzylamide 271

Glutaric acid-(4-dimethylamino-4-thiophen- 2-yl-cyclohexyl)-amide ethyl-(2-methyl- allyl)-amide 272

N,N-bis-(2-cyano-ethyl)-N′-(4- dimethylamino-4-thiophen-2-yl-cyclohexyl)- succinamide 273

Glutaric acid-benzyl-methyl-amide (4- dimethylamino-4-thiophen-2-yl-cyclohexyl)- amide 274

Glutaric acid-(2-benzyloxy-cyclopentyl)- amide (4-dimethylamino-4-thiophen-2-yl- cyclohexyl)-amide 275

Glutaric acid-(4-dimethylamino-4-thiophen- 2-yl-cyclohexyl)-amide 4-trifluoromethyl- benzylamide 276

N-(4-dimethylamino-4-thiophen-2-yl- cyclohexyl)-N′-[2-(4-phenoxy-phenyl)- ethyl]-succinamide 277

Glutaric acid-(4-dimethylamino-4-thiophen- 2-yl-cyclohexyl)-amide (3,3-diphenyl- propyl)-amide 278

4-(4-benzyl-piperidin-1-yl)-N-(4- dimethylamino-4-thiophen-2-yl-cyclohexyl)- 4-oxo-butyramide 279

N-(4-dimethylamino-4-thiophen-2-yl- cyclohexyl)-4-[4-hydroxy-4-(3- trifluoromethyl-phenyl)-piperidin-1-yl]-4- oxo-butyramide 280

Glutaric acid-(4-dimethylamino-4-thiophen- 2-yl-cyclohexyl)-amide 4-fluoro-2- trifluoromethyl-benzylamide 281

N-(4-dimethylamino-4-thiophen-2-yl- cyclohexyl)-N′-pentyl-succinamide 282

5-[4-(2-methoxy-naphthalen-1-ylmethyl)- piperazin-1-yl]-5-oxo-valeric acid (4- dimethylamino-4-thiophen-2-yl-cyclohexyl)- amide 283

N-(4-dimethylamino-4-thiophen-2-yl- cyclohexyl)-N′-(2-ethoxy-benzyl)-N′-furan- 2-ylmethyl-succinamide 284

Glutaric acid-(4-dimethylamino-4-thiophen- 2-yl-cyclohexyl)-amide (2-phenyl- cyclopropyl)-amide 285

N-[2-(3,4-dichloro-phenyl)-ethyl]-N′-(4- dimethylamino-4-phenyl-cyclohexyl)- succinamide 286

N-adamantan-1-ylmethyl-N′-(4- dimethylamino-4-phenyl-cyclohexyl)- succinamide 287

5-[4-(4-fluoro-phenyl)-3,6-dihydro-2H- pyridin-1-yl]-5-oxo-valeric acid (4- dimethylamino-4-thiophen-2-yl-cyclohexyl)- amide 288

2-[4-(4-dimethylamino-4-thiophen-2-yl- cyclohexylcarbamoyl)-butyrylamino]-4- methyl-valeric acid benzyl ester 289

{4-[4-(4-dimethylamino-4-thiophen-2-yl- cyclohexylcarbamoyl)-butyrylamino]- phenyl}-carbamic acid-tert-butylester 290

Glutaric acid-(4-dimethylamino-4-thiophen- 2-yl-cyclohexyl)-amide[2-(3-methoxy- phenyl)-ethyl]-amide 291

Glutaric acid-benzyl-ethyl-amide (4- dimethylamino-4-thiophen-2-yl-cyclohexyl)- amide 292

Glutaric acid-3-chloro-benzylamide (4- dimethylamino-4-thiophen-2-yl-cyclohexyl)- amide 293

Glutaric acid-(4-dimethylamino-4-thiophen- 2-yl-cyclohexyl)-amide (4-methyl- cyclohexyl)-amide 294

N-(4-dimethylamino-4-phenyl-cyclohexyl)- N′-[2-(1H-indol-3-yl)-ethyl]-N′-methyl- succinamide 295

Glutaric acid-2,5-dichloro-benzylamide (4- dimethylamino-4-thiophen-2-yl-cyclohexyl)- amide 296

Glutaric acid-(4-dimethylamino-4-thiophen- 2-yl-cyclohexyl)-amide[2-(3-fluoro- phenyl)-ethyl]-amide 297

N-(4-dimethylamino-4-phenyl-cyclohexyl)- N′-[2-(4-methoxy-phenoxy)-ethyl]- succinamide 298

N-(4-dimethylamino-4-thiophen-2-yl- cyclohexyl)-N′-[2-(ethyl-m-tolyl-amino)- ethyl]-succinamide 299

Glutaric acid-(4-benzyloxy-phenyl)-amide (4-dimethylamino-4-thiophen-2-yl- cyclohexyl)-amide 300

Glutaric acid-(4-dimethylamino-4-thiophen- 2-yl-cyclohexyl)-amide[2-(4-fluoro- phenyl)-ethyl]-amide 301

Glutaric acid-[2-(4-bromo-phenyl)-ethyl]- amide (4-dimethylamino-4-thiophen-2-yl- cyclohexyl)-amide 302

N-(4-dimethylamino-4-thiophen-2-yl- cyclohexyl)-N′-(4-phenoxy-phenyl)- succinamide 303

N-(4-dimethylamino-4-phenyl-cyclohexyl)- N′-[2-(3-trifluoromethyl-phenyl)-ethyl]- succinamide 304

Glutaric acid-[2-(4-chloro-phenyl)-propyl]- amide (4-dimethylamino-4-thiophen-2-yl- cyclohexyl)-amide 305

N-(4-dimethylamino-4-thiophen-2-yl- cyclohexyl)-N′-[2-(1H-indol-3-yl)-ethyl]-N′- methyl-succinamide 306

N-(4-dimethylamino-4-thiophen-2-yl- cyclohexyl)-N′-[2-(4-methoxy-phenoxy)- ethyl]-succinamide 307

Glutaric acid-(4-dimethylamino-4-thiophen- 2-yl-cyclohexyl)-amide (3-phenoxy-phenyl)- amide 308

N-(4-dimethylamino-4-phenyl-cyclohexyl)- N′-[2-(ethyl-m-tolyl-amino)-ethyl]- succinamide 309

Glutaric acid-[2-(5-bromo-2-methoxy- phenyl)-ethyl]-amide (4-dimethylamino-4- thiophen-2-yl-cyclohexyl)-amide 310

N-(4-dimethylamino-4-thiophen-2-yl- cyclohexyl)-N′-[2-(3-trifluoromethyl- phenyl)-ethyl]-succinamide 311

Glutaric acid-(4-dimethylamino-4-thiophen- 2-yl-cyclohexyl)-amide (1-methyl-3-phenyl- propyl)-amide 312

N-[2-(2,6-dichloro-benzylsulphanyl)-ethyl]- N′-(4-dimethylamino-4-thiophen-2-yl- cyclohexyl)-succinamide 313

Glutaric acid-(4-dimethylamino-4-thiophen- 2-yl-cyclohexyl)-amide (2,2-diphenyl- propyl)-amide 314

N-(4-dimethylamino-4-thiophen-2-yl- cyclohexyl)-N′-[3-(methyl-phenyl-amino)- propyl]-succinamide 315

N-(1-biphenyl-4-ylmethyl-pyrrolidin-3-yl)- N′-(4-dimethylamino-4-thiophen-2-yl- cyclohexyl)-N-methyl-succinamide 316

Glutaric acid-[4-(cyano-phenyl-methyl)- phenyl]-amide (4-dimethylamino-4- thiophen-2-ylcyclohexyl)-amide 317

Glutaric acid-(4-tert-butyl-cyclohexyl)- amide (4-dimethylamino-4-thiophen-2-yl- cyclohexyl)-amide 318

Glutaric acid-(4-sec-butyl-phenyl)-amide (4- dimethylamino-4-thiophen-2-yl-cyclohexyl)- amide 319

Glutaric acid-(4-butyl-phenyl)-amide (4- dimethylamino-4-thiophen-2-yl-cyclohexyl)- amide 320

N-(2-benzylsulphanyl-ethyl)-N′-(4- dimethylamino-4-thiophen-2-yl-cyclohexyl)- succinamide 321

N-(4-dimethylamino-4-thiophen-2-yl- cyclohexyl)-N′-(2-phenoxy-ethyl)- succinamide 322

Glutaric acid-(4-dimethylamino-4-thiophen- 2-yl-cyclohexyl)-amide (naphthalen-1- ylmethyl)-amide 323

Glutaric acid-3-bromo-benzylamide (4- dimethylamino-4-thiophen-2-yl-cyclohexyl)- amide 324

N-(4-dimethylamino-4-thiophen-2-yl- cyclohexyl)-N′-(3-phenyl-propyl)- succinamide 325

N-[2-(3-chloro-phenyl)-ethyl]-N′-(4- dimethylamino-4-phenyl-cyclohexyl)- succinamide 326

2-[3-(4-dimethylamino-4-thiophen-2-yl- cyclohexylcarbamoyl)-propionylamino]- propanoic acid benzylester 327

N-[2-(2-chloro-phenyl)-ethyl]-N′-(4- dimethylamino-4-phenyl-cyclohexyl)- succinamide 328

N-(4-dimethylamino-4-phenyl-cyclohexyl)- N′-[2-(3-fluoro-phenyl)-ethyl]-succinamide 329

Glutaric acid-(4-dimethylamino-4-thiophen- 2-yl-cyclohexyl)-amide (2-thiophen-2-yl- ethyl)-amide 330

Glutaric acid-(4-dimethylamino-4-thiophen- 2-yl-cyclohexyl)-amide[2-(4-phenoxy- phenyl)-ethyl]-amide 331

N-[2-(4-chloro-phenyl)-ethyl]-N′-(4- dimethylamino-4-phenyl-cyclohexyl)- succinamide 332

N-[2-(3-chloro-phenyl)-ethyl]-N′-(4- dimethylamino-4-thiophen-2-yl-cyclohexyl)- succinamide 333

N-benzyl-N′-(4-dimethylamino-4-thiophen- 2-yl-cyclohexyl)-N-ethyl-succinamide 334

Glutaric acid-[1-(2,6-dichloro-benzyl)- pyrrolidin-3-yl]-amide (4-dimethylamino-4- thiophen-2-yl-cyclohexyl)-amide 335

Glutaric acid-(4-dimethylamino-4-thiophen- 2-yl-cyclohexyl)-amide (3-phenyl-propyl)- amide 336

Glutaric acid-(4-dimethylamino-4-thiophen- 2-yl-cyclohexyl)-amide[2-(1H-indol-3-yl)- ethyl]-amide 337

5-(3,4-dihydro-1H-isoquinolin-2-yl)-5-oxo- valeric acid (4-dimethylamino-4-thiophen-2- yl-cyclohexyl)-amide 338

{[4-(4-dimethylamino-4-thiophen-2-yl- cyclohexylcarbamoyl)-butyryl]-methyl- amino}-acetic acid benzylester 339

N-(4-dimethylamino-4-thiophen-2-yl- cyclohexyl)-N′-[2-(4-phenoxy-phenyl)- ethyl]-succinamide 340

Glutaric acid-(4-dimethylamino-4-thiophen- 2-yl-cyclohexyl)-amide (2-phenyl- cyclopropyl)-amide

Selected examples have also been synthesised on a larger scale.

Example 341 N-[-(4-chlorobenzyl)-4-dimethylaminocyclohexyl]-N′-furan-2-yl-methylsuccinic acid amide hydrochloride, non-polar diastereoisomer

A solution of 5.0 ml C-furan-2-yl-methylamine and 6.7 ml dilsopropylethylamine in 25 ml THF p.a. was added dropwise to 3.92 g succinic acid anhydride in 40 ml THF p.a. and the solution stirred over night. After addition of 25 ml two-molar hydrochloric acid, extraction was carried out three times with 40 ml dichloromethane in each case, the extracts dried over magnesium sulphate, filtered and evaporated. 7.0 g N-furan-2-yl-methylsuccinic acid were obtained.

1.0 g 1-(3-chlorobenzyl)-N,N-dimethylcyclohexane-1,4-diamine, obtained as a cis/trans-mixture from 4-(3-chlorobenzyl)-4-dimethylaminocyclohexanone by reaction with hydroxylamine and reduction of the oxime obtained with lithium aluminium hydride (WO 02090317), dissolved in 5 ml DMF, was added to 0.74 g N-furan-2-yl-methylsuccinic acid at 0° C. and 0.59 ml N,N-diisopropylcarbodiimide followed by 0.5 g 1-hydroxybenzotriazole (HOBt) were added while stirring. After 3 hours in an ice bath, the mixture was stirred overnight at room temperature. For working up, one-molar sodium carbonate solution was added (pH>10) and the crude product (1.75 g) was isolated by extraction with ethyl acetate/THF (V:V=1:1), with subsequent drying over sodium sulphate and evaporation. The main fraction, obtained after column chromatography on silica gel (3.0×20 cm) with 250 ml diethyl ether, diethyl ether/methanol (V:V=4:1) and diethyl ether/methanol (V:V=1:1), of 718 mg was dissolved in 50 ml 2-butanone, 50 ml ethyl acetate and 2 ml methanol and, by adding 29 μl water and 200 μl chlorotrimethylsilane, converted into the corresponding hydrochloride of the N-[4-(3-chlorobenzyl)-4-dimethylaminocyclohexyl]-N′-furan-2-yl-methylsuccinic acid amide (648 mg of white solid, mp. 233-234.5° C.).

Example 342 N-[4-(3-chlorobenzyl)-4-dimethylaminocyclohexyl]-N′-furan-2-yl-methylsuccinic acid amide hydrochloride, polar diastereoisomer

As described for Example 341, 357 mg of the polar diastereoisomer of N-[4-(3-chlorobenzyl)-4-dimethylaminocyclohexyl]-N′-furan-2-yl-methylsuccinic acid amide were also obtained, which, dissolved in 25 ml 2-butanone, were converted into the corresponding hydrochloride by adding 14.4 μl water and 100 μl chlorotrimethylsilane (230 mg of white solid, mp. 186-188° C.).

Example 343 Glutaric acid (4-benzyl-4-dimethylaminocyclohexyl)amide [2-(2-fluorophenyl)ethyl]amide hydrochloride, non-polar diastereoisomer

As described for Example 341, 0.95 mg 4-[2-(2-fluorophenyl)ethylcarbamoyl]butyric acid and 0.87 1-benzyl-N,N-dimethylcyclohexane-1,4-diamine were converted in 5 ml DMF in the presence of 0.59 ml N,N-diisopropylcarbodiimide and 0.50 g 1-hydroxybenzotriazole and the crude product (1.65 g yellow solid) similarly isolated. 720 mg of the non-polar diastereoisomer of glutaric acid (4-benzyl-4-dimethylaminocyclohexyl)amide was obtained by column chromatography on silica gel (3.0×20 cm) with 450 ml diethyl ether, followed by 450 ml diethyl ether/methanol (V:V=4:1) and 450 ml diethyl ether/methanol (V:V=1:1), was dissolved in 25 ml 2-butanone, 25 ml ethyl acetate and converted into the corresponding hydrochloride by adding 28 μl water and 198 μl chlorotrimethylsilane (657 mg of vitreous solid).

Example 344 Glutaric acid (4-benzyl-4-dimethylaminocyclohexyl)amide [2-(2-fluorophenyl)ethyl]amide hydrochloride, polar diastereoisomer

As described for Example 343, 260 mg of the polar diastereoisomer of glutaric acid (4-benzyl-4-dimethylaminocyclohexyl)amide were also obtained, which were dissolved in 5 ml 2-butanone and 45 ml ethyl acetate and converted into the corresponding hydrochloride by adding 10 μl water and 71 μl chlorotrimethylsilane (110 mg of vitreous solid).

Example 345 N-[4-(3-chlorobenzyl)-4-dimethylaminocyclohexyl]-N′-[2-(4-chlorophenyl)ethyl]succinic acid amide hydrochloride, non-polar diastereoisomer

As described for Example 341, 0.96 mg N-[2-(4-chlorophenyl)ethyl]succinic acid and 1.0 g 4-(3-chlorobenzyl)-4-dimethylaminocyclohexanone were converted in 5 ml DMF in the presence of 0.59 ml N,N-diisopropylcarbodiimide and 0.5 g 1-hydroxybenzotriazole and the crude product (2.23 g yellow solid) similarly isolated. 947 mg of the non-polar diastereoisomer of N-[4-(3-chlorobenzyl)-4-dimethylaminocyclohexyl]-N′-[2-(4-chlorophenyl)ethyl]succinic acid amide were obtained by column chromatography on silica gel (3.0×20 cm) with 200 ml diethyl ether, followed by 200 ml diethyl ether/methanol (V:V=5:1). 300 mg of this were dissolved in 5 ml 2-butanone, 10 ml ethyl acetate and 1 ml methanol and 10.7 μl water and 76 μl chlorotrimethylsilane were added, the batch evaporated to dryness, the residue stirred over 3 days at room temperature with 10 ml butanone and 10 diisopropylether and the precipitated hydrochloride isolated by filtration and dried (200 mg white solid).

Example 346 N-[4-(3-chlorobenzyl)-4-dimethylaminocyclohexyl]-N′-[2-(4-chlorophenyl)ethyl]succinic acid amide hydrochloride, polar diastereoisomer

As described for Example 345, 360 mg of the polar diastereoisomer of N-[4-(3-chlorobenzyl)-4-dimethylaminocyclohexyl]-N′-[2-(4-chlorophenyl)ethyl]succinic acid amide were also obtained, which were dissolved in 25 ml 2-butanone and 10 ml ethyl acetate and converted into the corresponding hydrochloride by adding 12.5 μl water, 88 μl chlorotrimethylsilane and 10 ml diisopropylether (236 mg of white solid, mp 186-187.5° C.).

Example 347 Glutaric acid (4-benzyl-4-dimethylaminocyclohexyl)amide [2-4(-chlorophenyl)ethyl]amide hydrochloride, non-polar diastereoisomer

As described for Example 341, 0.87 mg 4-[2-(4-chlorophenyl)ethyl-carbamoyl]butyric acid and 1.0 g 4-benzyl-4-dimethylaminocyclohexanone were converted in 5 ml DMF in the presence of 0.59 ml N,N-diisopropylcarbodiimide and 0.5 g 1-hydroxybenzotriazole and the crude product (1.80 g) similarly isolated. 900 mg of the non-polar diastereoisomer of glutaric acid (4-benzyl-4-dimethylaminocyclohexyl)amide [2-4(-chlorophenyl)ethyl] amide were obtained by chromatography on silica gel (3.0×20 cm) with 200 ml diethyl ether, followed by 200 ml diethyl ether/methanol (V:V=5:1), was dissolved in 20 ml 2-butanone and 20 ml ethyl acetate and converted into the corresponding hydrochloride by adding 33.5 μl water and 236 μl chlorotrimethylsilane and then evaporating to dryness (980 mg of vitreous solid).

Example 348 Glutaric acid (4-benzyl-4-dimethylaminocyclohexyl)amide [2-(4-chlorophenyl)ethyl]amide hydrochloride, polar diastereoisomer

As described for Example 347, 335 mg of the polar diastereoisomer of glutaric acid (4-benzyl-4-dimethylaminocyclohexyl)amide [2-(4-chlorophenyl)ethyl]amide were obtained, which, dissolved in 30 ml 2-butanone, 30 ml ethyl acetate and 2 ml methanol, were converted into the corresponding hydrochloride by adding 12.5 μl water, 88 μl chlorotrimethylsilane and 10 ml diisopropylether (255 mg of white solid).

Tests on the Efficacy of the Compounds According to the Invention:

Measurement of ORL1 Binding

The cyclohexane derivatives of general formula I were examined in a receptor binding assay with ³H-nociceptin/orphanin FQ with membranes of recombinant CHO-ORL1 cells. This test system was carried out according to the methods presented by Ardati et al (Mol. Pharmacol., 51, 1997, pp. 816-824). The concentration of ³H-nociceptin/orphanin FQ was 0.5 nM in these tests. The binding assays were carried out with 20 μg membrane protein per 200 μl batch in 50 mM Hepes, pH 7.4, 10 mM MgCl₂ and 1 mM EDTA. The binding with the ORL1 receptor was determined by using 1 mg WGA-SPA beads (Amersham-Pharmacia, Freiburg), by incubation of the batch for one hour at RT and subsequent measurement in the Trilux scintillation counter (Wallac, Finland). The affinity is shown in Table 1 as a nanomolar K_(i) value in or % inhibition at c=1 μM.

Measurement of μ-Binding

The receptor affinity for human p-opiate receptor was determined in a homogenous batch in microtitre plates. For this purpose, dilution series of the respective substituted cyclohexyl-1,4-diamine derivative to be tested were incubated with a receptor membrane preparation (15-40 μg protein per 250 μl incubation batch) of CHO-K1 cells, which express the human μ-opiate receptor (RB-HOM receptor membrane preparation from NEN, Zaventem, Belgium) in the presence of 1 nmol/l of the radioactive ligand [³H]-naloxone (NET719, NEN, Zaventem, Belgium) and 1 mg WGA-SPA beads (wheat germ agglutinin SPA beads from Amersham/Pharmacia, Freiburg, Germany) in a total volume of 250 μl for 90 minutes at room temperature. 50 mmol/l tris-HCI were added as an incubation buffer with 0.05% by weight sodium azide and 0.06% by weight bovine serum albumin. 25 μmol/l naloxone were also added to determine the non-specific binding. At the end of the 90-minute incubation period, the microtitre plates were centrifuged off for 20 minutes at 1000 g and the radioactivity measured in a β-counter (Microbeta-Trilux, PerkinElmer Wallac, Freiburg, Germany). The percentage displacement of the radioactive ligand from its binding with the human p-opiate receptor at a concentration of the test substances of 1 μmol/l was determined and given as a percentage inhibition (% inhibition) of the specific binding. IC₅₀ inhibition concentrations, which bring about a 50% displacement of the radioactive ligand, were partially calculated by taking as a basis the percentage displacement by various concentrations of the compounds of general formula I to be tested. Ki values for the test substances were obtained as a result of conversion by means of the Cheng-Prusoff equation.

Measurement of Serotonin Re-Uptake

In order to carry out these in vitro studies, synaptosomes were freshly isolated from areas of rats' brains. In each case, what is known as a “P₂” fraction, which was prepared in accordance with Gray and Whittaker's directions (E. G. Gray and V. P. Whittaker (1962) J. Anat. 76, 79-88), was used. For the 5HT-uptake, these vesicular particles were isolated from the medulla+pons region of male rats' brains.

A detailed description of the method can be found in the literature (M. Ch. Frink, H.-H. Hennies, W. Englberger, M. Haurand and B. Wilffert (1996) Arzneim.-Forsch./Drug Res. 46 (III), 11, 1029-1036).

Measurement of Noradrenalin Re-Uptake

In order to carry out these in vitro studies, synaptosomes were freshly isolated from rat brain areas. In each case, what is known as a “P₂” fraction, which was prepared in accordance with Gray and Whittaker's directions (E. G. Gray and V. P. Whittaker (1962) J. Anat. 76, 79-88), was used. For the NA-uptake, these vesicular particles were isolated from the hypothalamus of male rats' brains.

A detailed description of the method can be found in the literature (M. Ch. Frink, H. H. Hennies, W. Englberger, M. Haurand and B. Wilffert (1996) Arzneim.-Forsch./Drug Res. 46 (III), 11, 1029-1036).

The following binding data was determined, by way of example:

ORL1-binding, [1 μM], Example % inhibition 249 49 250 76 251 96 252 88 253 92 254 88 255 69 256 95 257 94 258 68 259 73 260 80 261 90 262 57 263 79 264 99 265 77 266 96 267 95 268 98 269 86 270 92 271 78 272 39 273 96 274 64 275 85 276 98 277 86 278 96 279 82 280 96 281 77 282 82 283 76 284 84 285 99 286 72 287 79 288 75 289 86 290 95 291 78 292 93 293 81 294 100 295 98 296 97 297 74 298 73 299 90 300 95 301 99 302 72 303 99 304 98 305 99 306 72 307 98 308 71 309 100 310 98 311 90 312 100 313 71 314 88 315 60 316 77 317 91 318 94 319 97 320 98 321 90 322 98 323 97 324 96 325 98 326 91 327 93 328 94 329 97 330 99 331 92 332 98 333 92 334 95 335 94 336 99 337 96 338 98 339 98 340 84

μ-binding, [1 μM], Example % inhibition 15 59 31 53 40 57 42 64 55 50 59 55 63 65 64 67 66 57 69 58 74 56 76 54 77 62 78 54 80 51 82 60 90 89 95 56 97 59 110 55 115 59 116 50 117 68 118 59 119 70 120 58 121 50 124 80 125 87 127 64 128 64 129 56 130 60 131 66 132 70 136 62 141 58 142 70 143 57 144 67 145 66 146 58 147 66 148 64 149 54 150 67 151 90 152 68 153 67 154 57 155 66 156 69 157 54 159 80 160 62 161 52 162 50 163 51 164 58 167 59 169 60 170 68 171 67 172 58 173 90 174 72 175 84 176 56 177 56 178 60 179 56 180 59 181 50 182 53 183 61 184 51 185 57 186 55 187 53 188 50 189 61 190 54 191 59 192 54 193 51 194 68 195 51 196 50 197 74 198 62 199 50 200 55 201 69 202 67 203 56 204 52 205 51 206 56 207 57 208 50 209 67 210 57 211 56 212 77 213 73 214 58 215 54 216 65 217 54 218 62 219 60

5HT-uptake [10 μM], Example % inhibition 1 93 2 95 3 94 4 92 5 93 6 96 7 93 8 92 9 93 10 92 11 92 12 92 13 92 14 95 15 92 16 97 17 93 18 94 19 93 20 92 21 95 22 95 23 92 24 92 25 97 26 93 27 95 28 92 29 94 30 93 31 97 32 99 33 95 34 97 35 94 36 96 37 95 38 95 39 94 40 94 41 92 42 97 43 98 44 94 45 92 46 92 47 93 48 94 49 92 50 92 51 92 52 96 53 93 54 95 56 95 57 93 58 93 60 93 61 92 62 100 63 94 64 96 65 92 66 94 67 98 68 98 70 93 71 92 72 95 73 93 74 96 75 97 76 96 79 96 81 92 82 92 83 93 84 95 85 94 86 92 87 96 88 97 89 94 90 96 91 92 92 92 93 92 94 92 95 93 96 94 98 92 99 94 100 92 101 94 102 94 103 94 104 93 105 92 106 93 107 95 108 94 110 100 111 96 112 96 113 97 114 99 122 93 123 92 126 93 133 93 134 92 135 92 137 94 138 92 139 93 140 93 141 94 165 92 168 92

NA-uptake [10 μM], Example % inhibition 1 71 2 87 3 89 4 89 5 80 6 91 7 91 8 85 9 91 10 78 11 77 12 95 13 72 14 78 15 85 16 86 17 82 18 84 19 74 20 90 21 83 22 93 23 92 24 91 25 95 26 79 27 92 28 81 29 91 30 96 31 102 32 97 33 99 34 87 35 95 36 93 37 100 38 79 39 90 40 96 41 90 42 97 43 96 44 84 45 77 46 89 47 73 48 97 49 98 50 89 51 77 52 88 53 94 54 90 56 96 57 100 58 79 60 71 61 93 62 86 63 94 64 102 65 84 66 92 67 96 68 85 70 96 71 94 72 70 73 87 74 98 75 99 76 101 79 95 81 91 82 94 83 105 84 96 85 100 86 76 87 94 88 102 89 98 90 109 91 101 92 89 93 75 94 86 95 99 96 87 98 74 99 99 100 77 101 77 102 105 103 108 104 84 105 90 106 98 107 106 108 100 110 95 111 97 112 101 113 94 114 106 122 102 123 99 126 84 133 97 134 101 135 96 137 83 138 84 139 95 140 77 141 99 165 94 168 96

Parenteral Solution of a Substituted cyclohexyl-1,4-diamine Derivative According to the Invention

38 g of one of the substituted cyclohexyl-1,4-diamine derivatives according to the invention, here Example 1, were dissolved at room temperature in 1 l water for injection purposes and then adjusted to isotonic conditions for injection purposes by adding anhydrous glucose.

The foregoing description and examples have been set forth merely to illustrate the invention and are not intended to be limiting. Since modifications of the described embodiments incorporating the spirit and substance of the invention may occur to persons skilled in the art, the invention should be construed broadly to include all variations within the scope of the appended claims and equivalents thereof. 

1. A cyclohexyl-1,4-diamine compound corresponding to formula I,

wherein n represents 1, 2, 3, 4 or 5 R¹ and R² independently of one another represent H; saturated or unsaturated, branched or unbranched, singly or multiply substituted or unsubstituted C₁₋₅ alkyl; singly or multiply substituted or unsubstituted C₃₋₈ cycloalkyl; or singly or multiply substituted or unsubstituted aryl, C₃₋₈ cycloalkyl or heteroaryl bound by C₁₋₃ alkyl; or R¹ and R² together form a ring and represent CH₂CH₂OCH₂CH₂, CH₂CH₂NR¹⁰CH₂CH₂ or (CH2)₃₋₆, wherein R¹⁰ represents H; saturated or unsaturated, branched or unbranched, singly or multiply substituted or unsubstituted C₁₋₅ alkyl singly or multiply substituted or unsubstituted C₃₋₈ cycloalkyl; singly or multiply substituted or unsubstituted aryl or heteroaryl; or singly or multiply substituted or unsubstituted aryl, C₃₋₈ cycloalkyl or heteroaryl bound by C₁₋₃ alkyl; substituted or unsubstituted C(O)phenyl, C(O)heteroaryl, C(O)C₁₋₅ alkyl; R³ represents saturated or unsaturated, branched or unbranched, singly or multiply substituted or unsubstituted C₁₋₅ alkyl; singly or multiply substituted or unsubstituted C₃₋₈ cycloalkyl; unsubstituted or singly or multiply substituted aryl or heteroaryl; unsubstituted or singly or multiply substituted aryl, heteroaryl or C₃₋₈ cycloalkyl bound by a C₁₋₃ alkyl group; R⁴ represents —(CR⁶R⁷)_(p)R⁸, wherein p represents 0, 1, 2, 3 or 4; R⁶ represents H or saturated or unsaturated, branched or unbranched, unsubstituted or singly or multiply substituted C₁₋₅ alkyl; R⁷ represents H, saturated or unsaturated, branched or unbranched, unsubstituted or singly or multiply substituted C₁₋₅ alkyl or COOR⁹; or R⁶ and R⁷ together form a ring and represent (CH₂)_(k)CHR⁸(CH₂)_(m), where k =1, 2, or 3 and m =1 or 2; R⁸ represents respectively saturated or unsaturated, branched or unbranched, unsubstituted or singly or multiply substituted C₁₋₆ alkyl; unsubstituted or singly or multiply substituted C₃₋₈ cycloalkyl, aryl or heteroaryl; R⁹ represents H or C₁₋₅ alkyl; R⁵ represents H or —(CH₂)₁R⁸, wherein l represents 1, 2 or 3 or R⁵ and R⁴ together form a ring and represent CH₂CHR¹⁴OCHR¹⁴CH₂, CH₂CH₂SCH₂CH₂ CH₂CH₂NR¹¹CH₂CH₂, (CR¹²R¹³)₃₋₆ or

wherein R¹¹ represents H; saturated or unsaturated, branched or unbranched, singly or multiply substituted or unsubstituted C₁₋₅ alkyl; saturated or unsaturated, singly or multiply substituted or unsubstituted C₃₋₈ cycloalkyl; singly or multiply substituted or unsubstituted aryl or heteroaryl; or singly or multiply substituted or unsubstituted aryl, C₃₋₈ cycloalkyl or heteroaryl bound by C₁₋₃ alkyl; R¹² represents H; saturated or unsaturated, branched or unbranched, singly or multiply substituted or unsubstituted C₁₋₅ alkyl; OH; unsubstituted or singly or multiply substituted C(O)phenyl; singly or multiply substituted or unsubstituted C₃₋₈ cycloalkyl; respectively singly or multiply substituted or unsubstituted aryl or heteroaryl; or singly or multiply substituted or unsubstituted aryl, C₃₋₈ cycloalkyl or heteroaryl bound by C₁₋₃ alkyl; and R¹³ represents H or OH or together with R¹² via the same C atom or an adjacent C atom forms a five-membered or six-membered ring which may contain heteroatoms, be saturated or unsaturated, substituted or unsubstituted or be part of a polycyclic system; R¹⁴ represents respectively saturated or unsaturated, branched or unbranched, singly or multiply substituted or unsubstituted C₁₋₃ alkyl; or an acid, base or a physiologically acceptable salt thereof.
 2. The compound of claim 1, wherein said compound is present in the form of a pure enantiomer or pure diastereoisomer.
 3. The compound of claim 1, wherein said compound is present in the form of a mixture of stereoisomers.
 4. The compound of claim 1, wherein said compound is present in the form of a racemic mixture.
 5. A cyclohexyl-1,4-diamine compound according to claim 1, wherein R¹ and R² independently of one another represent H; saturated or unsaturated, branched or unbranched, singly or multiply substituted or unsubstituted C₁₋₅ alkyl; or R¹ and R² together form a ring and represent CH₂CH₂OCH₂CH₂, CH₂CH₂NR¹⁰CH₂CH₂ or (CH2)₃₋₆, wherein R¹⁰ represents H; saturated or unsaturated, branched or unbranched, singly or multiply substituted or unsubstituted C₁₋₅ alkyl.
 6. A cyclohexyl-1,4-diamine compound according to claim 1, wherein R¹ and R² independently of one another represent CH₃ or H, wherein R¹ and R² do not simultaneously represent H, or R¹ and R² together form a ring and represent CH₂CH₂OCH₂CH₂ or (CH₂)₆.
 7. A cyclohexyl-1,4-diamine compound according to claim 1, wherein R³ represents unsubstituted or singly or multiply substituted cyclopentyl, cyclohexyl, phenyl, benzyl, naphthyl, anthracenyl, thiophenyl, benzothiophenyl, furyl, benzofuranyl, benzodioxolanyl, indolyl, indanyl, benzodioxanyl, pyrrolyl, pyridyl, pyrimidyl or pyrazinyl; respectively unsubstituted or singly or multiply substituted C₅₋₆ cycloalkyl, phenyl, naphthyl, anthracenyl, thiophenyl, benzothiophenyl, pyridyl, furyl, benzofuranyl, benzodioxolanyl, indolyl, indanyl, benzodioxanyl, pyrrolyl, pyrimidyl or pyrazinyl bound by a saturated, unbranched C₁₋₂ alkyl.
 8. A cyclohexyl-1,4-diamine compound according to claim 1, wherein R³ represents unsubstituted or singly or multiply substituted phenyl, furyl, thiophenyl, naphthyl, benzyl, benzofuranyl, indolyl, indanyl, benzodioxanyl, benzodioxolanyl, pyridyl, pyrimidyl, pyrazinyl or benzothiophenyl; unsubstituted or singly or multiply substituted phenyl, furyl or thiophenyl bound by a saturated, unbranched C₁₋₂ alkyl group.
 9. A cyclohexyl-1,4-diamine compound according to claim 1, wherein R³ represents substituted or unsubstituted phenyl, thiophenyl, pyridyl or benzyl, more preferably 4-methylbenzyl, 3-chlorobenzyl, 4-chlorobenzyl, 3-methylbenzyl, benzyl, phenyl, thiophenyl or 3-fluorophenyl.
 10. A cyclohexyl-1,4-diamine compound according to claim 1, wherein n represents 2 or
 3. 11. A cyclohexyl-1,4-diamine compound according to claim 1, wherein R ⁴ represents —(CR⁶R⁷)_(p)R⁸ and R⁵ represents H.
 12. A cyclohexyl-1,4-diamine compound according to claim 1, wherein R⁴ represents (CH₂)_(p)R⁸ and R⁵ represents —(CH₂)_(l)R⁸.
 13. A cyclohexyl-1,4-diamine compound according to claim 1, wherein R⁴ and R⁵ together represent CH₂CHR¹⁴OCHR¹⁴CH₂, CH₂CH₂SCH₂CH₂, CH₂CH₂NR¹¹CH₂CH₂ (CR¹²R¹³)₃₋₆ or


14. A cyclohexyl-1,4-diamine compound according to claim 1, wherein R⁶ represents H and R⁷ represents H, CH₃, unsubstituted or singly or multiply substituted benzyl, or COOR⁹ or R⁶ and R⁷ together form a ring and represent (CH₂)_(k)CHR⁸(CH₂)_(m).
 15. A cyclohexyl-1,4-diamine compound according to claim 1, wherein R⁸ represents saturated or unsaturated, branched or unbranched, unsubstituted or singly or multiply substituted C₁₋₆ alkyl; unsubstituted or singly or multiply substituted cyclobutyl, cyclopropyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, anthracenyl, indolyl, naphthyl, benzofuranyl, benzothiophenyl, indanyl, benzodioxanyl, benzodioxolanyl, acenaphthyl, carbazolyl, phenyl, thiophenyl, furyl, pyrrolidinyl, tetrahydrofuryl, piperazinyl, pyridyl, pyrrolyl, pyrazinyl or pyrimidyl, fluorenyl, fluoranthenyl, benzothiazolyl, benzotriazolyl or benzo[1,2,5]thiazolyl or 1,2-dihydroacenaphthenyl, pyridinyl, furanyl, benzofuranyl, pyrazolinonyl, oxopyrazolinonyl, dioxolanyl, adamantyl, pyrimidinyl, quinolinyl, isoquinolinyl, phthalazinyl or quinazolinyl.
 16. A cyclohexyl-1,4-diamine compound according to claim 1, wherein R⁸ represents saturated or unsaturated, branched or unbranched, unsubstituted or singly or multiply substituted C₁₋₆ alkyl; unsubstituted or singly or multiply substituted pyrrolidinyl, morpholinyl, tetrahydrofuryl, tetrahydronaphthyl, dihydroindolyl, pyridyl, thienyl, piperazinyl, naphthyl, indanyl, quinolinyl, cyclopropyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, adamantyl, furyl, benzofuryl, phenyl or indolyl.
 17. A cyclohexyl-1,4-diamine compound according to claim 1, wherein said compound is selected from the group consisting of: N-[1-(2,6-dichloro-benzyl)-pyrrolidin-3-yl]-N′-[4-dimethylamino-4-(4-methyl-benzyl)-cyclohexyl]-succinamide; N-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-(2-oxo-tetrahydro-furan-3-yl)-succinamide; N-[4-(4-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-(3,3-diphenyl-propyl)-succinamide; N-[4-dimethylamino-4-(4-methyl-benzyl)-cyclohexyl]-4-[4-(7-methoxy-benzo[1,3]dioxol-5-yl-methyl)-piperazin-1-yl]-4-oxo-butyramide; N-[4-(4-chloro-benzyl)-4-dimethylamino-cyclohexyl]-4-(3,6-dihydro-2H-pyridin-1-y1)-4-oxo-butyramide; N-[4-dimethylamino-4-(4-methyl-benzyl)-cyclohexyl]-4-oxo-4-(4-m-tolyl-piperazin-1-yl)-butyramide; 2-{3-[4-(4-chloro-benzyl)-4-dimethylamino-cyclohexylcarbamoyl]-propionylamino}-propanoic acid ethylester; N-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-4-(8-fluoro-1,3,4,5-tetrahydro-pyrido[4,3-b]indol-2-yl)-4-oxo-butyramide; 3-{3-[4-dimethylamino-4-(4-methyl-benzyl)-cyclohexylcarbamoyl]-propionylamino}-propanoic acid ethylester; N-[4-dimethylamino-4-(4-methyl-benzyl)-cyclohexyl]-4-[4-(5-methyl-pyrazin-2-carbonyl)-piperazin -1-yl]-4-oxo-butyramide; N-[4-dimethylamino-4-(4-methyl-benzyl)-cyclohexyl]-N′-methyl-N′-[2-(2,2,2-trifluoro-acetylamino)-ethyl ]-succinamide; N-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-(2-pyridin-2-yl-ethyl)-succinamide; N-[4-(4-chloro-benzyl)-4-dimethylamino-cyclohexyl]-4-oxo-4-thiomorpholin-4-yl-butyramide; N-[4-(4-chloro-benzyl)-4-dimethylamino-cyclohexyl]-4-[4-(5-methyl-pyrazin-2-carbonyl)-piperazin -1-yl]-4-oxo-butyramide; N-[4-dimethylamino-4-(3-methyl-benzyl)-cyclohexyl]-N′-(2-thiophen-2-yl-ethyl)-succinamide; N-[4-(4-chloro-benzyl)-4-dimethylamino-cyclohexyl]-4-[4-(4-ethoxy-phenyl)-piperazin-1-yl]-4-oxo-butyramide; N-allyl-N′-[4-(4-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N-methyl-succinamide; 5-[4-(2,5-dimethoxy-benzyl)-piperazin-1-yl]-5-oxo-valeric acid (4-benzyl-4-dimethylamino-cyclohexyl)-amide; 4-(3,6-dihydro-2H-pyridin-1-yl)-N-[4-dimethylamino-4-(4-methyl-benzyl)-cyclohexyl]-4-oxo-butyramide; N-[4-dimethylamino-4-(3-methyl-benzyl)-cyclohexyl]-4-(4-methyl-piperidin-1-yl)-4-oxo-butyramide; N-[4-dimethylamino-4-(4-methyl-benzyl)-cyclohexyl]-4-oxo-4-(4-pyridin-2-yl-piperazin-1-yl)-butyramide; ({3-[4-dimethylamino-4-(3-methyl-benzyl)-cyclohexylcarbamoyl]-propionyl}-methyl-amino)-acetic acid benzyl ester; 4-[4-(2,6-dichloro-benzyl)-piperazin-1-yl]-N-[4-dimethylamino-4-(3-methyl-benzyl)-cyclohexyl]-4-oxo-butyramide; {[4-(4-benzyl-4-dimethylamino-cyclohexylcarbamoyl)-butyryl]-methyl-amino}-acetic acid tert butyl ester; 5-[4-(2-fluoro-5-methoxy-benzyl)-piperazin-1-yl]-5-oxo-valeric acid (4-benzyl-4-dimethylamino-cyclohexyl)-amide; N-[4-(4-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-(3-methoxy-propyl)-succinamide; 4-[4-(4-acetyl-phenyl)-piperazin-1-yl]-N-[4-dimethylamino-4-(4-methyl-benzyl)-cyclohexyl]-4-oxo-butyramide; 4-{3-[4-dimethylamino-4-(4-methyl-benzyl)-cyclohexylcarbamoyl]-propionyl}-piperazin-1-carboxylic acid-tert-butylester; N-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-(tetrahydro-furan-2-ylmethyl)-succinamide; 2-{3-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexylcarbamoyl]-propionylamino}-propanoic acid ethylester; N-(3-bromo-benzyl)-N′-[4-dimethylamino-4-(3-methyl-benzyl)-cyclohexyl]-succinamide; 3-(4-chloro-phenyl)-2-{3-[4-dimethylamino-4-(4-methyl-benzyl)-cyclohexylcarbamoyl]-propionylamino}-prop anoic acid methylester; N-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-4-[4-(5-methyl-pyrazin-2-carbonyl)-piperazin-1-yl]-4-oxo-butyramide; N-[4-(4-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-naphthalen-1-ylmethyl-succinamide; N-[4-dimethylamino-4-(3-methyl-benzyl)-cyclohexyl]-4-[4-(3-fluoro-4-methoxy-benzyl)-piperazin-1-yl]-4-oxo-butyramide; N-[4-dimethylamino-4-(4-methyl-benzyl)-cyclohexy]N′-[2-(1H-indol-3-yl)-ethyl]-N′-methyl-succinamide; (4-{3-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexylcarbamoyl]-propionylamino}-benzyl)-phosphonic acid diethylester; N-[4-dimethylamino-4-(4-methyl-benzyl)-cyclohexyl]-N′-methyl-N′-(2-pyridin-2-yl-ethyl)-succinamide; N-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-4-(3,6-dihydro-2H-pyridin-1-yl)-4-oxo-butyramide; N-[4-dimethylamino-4-(3-methyl-benzyl)-cyclohexyl]-N′-(1-methyl-3-phenyl-propyl)-succinamide; 5-[4-(5-methyl-pyrazin-2-carbonyl)-piperazin-1-yl]-5-oxo-valeric acid (4-benzyl-4-dimethylamino-cyclohexyl)-amide; N-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-(2-chloro-6-methyl-benzyl)-succinamide; N-allyl-N′-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N-methyl-succinamide; N-[4-(4-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-cyclopentyl-succinamide; N-[4-dimethylamino-4-(4-methyl-benzyl)-cyclohexyl]-N′-(tetrahydro-furan-2-ylmethyl)-succinamide; (4-{3-[4-dimethylamino-4-(3-methyl-benzyl)-cyclohexylcarbamoyl]-propionylamino}-benzyl)-phosphonic acid diethylester; N-[4-(4-chloro-benzyl)-4-dimethylamino-cyclohexyl]-4-[4-(2-methoxy-phenyl)-piperazin-1-yl]-4-oxo-butyramide; N-[4-dimethylamino-4-(3-methyl-benzyl)-cyclohexyl]-4-[4-(3-methoxy-phenyl)-piperazin-1-yl]-4-oxo-butyramide; N-[4-(4-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-(3,5-difluoro-benzyl)-succinamide; N-[4-(4-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-(2-methyl-benzyl)-succinamide; N-[4-dimethylamino-4-(4-methyl-benzyl)-cyclohexyl]-4-oxo-4-{4-[(2,2,2-trifluoro-acetylamino)-methyl]-piperidin-1-yl}-butyramide; N-[4-(4-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-[2-(1H-indol-3-yl)-ethyl]-succinamide; N-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-[2-(1H-indol-3-yl)-ethyl]-N′-methyl-succinamide; 5-[4-(7-methoxy-benzo[1,3]dioxo1-5-ylmethyl)-piperazin-1-yl]-5-oxo-valeric acid (4-benzyl-4-dimethylamino-cyclohex)/1)-amide; N-benzyl-N′-[4-dimethylamino-4-(3-methyl-benzyl)-cyclohexyl]-N-(2-hydroxy-ethyl)-succinamide; 5-[4-(2,3-dimethyl-phenyl)-piperazin-1-yl]-5-oxo-valeric acid (4-benzyl-4-dimethylamino-cyclohexyl)-amide; N-[4-(4-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-[2-(1H-indol-3-yl)-ethyl]-N′-methyl-succinamide; N-[4-dimethylamino-4-(4-methyl-benzyl)-cyclohexyl]-4-[4-(2,3-dimethyl-phenyl)-piperazin-1-yl]-4-oxo-butyramide; Glutaric acid-(4-benzyl-4-dimethylamino-cyclohexyl)-amide (1,2,3,4-tetrahydro-naphthalen-1-yl)-amide; N-[4-(4-chloro-benzyl)-4-dimethylamino-cyclohexyl]-4-(4-methyl-piperidin-1-yl)-4-oxobutyramide; 2-{3-[4-dimethylamino-4-(4-methyl-benzyl)-cyclohexylcarbamoyl]-propionylamino}-propanoic acid-tert-butylester; 5-(4-cycloheptyl-piperazin-1-yl)-5-oxo-valeric acid (4-benzyl-4-dimethylamino-cyclohexyl)-amide; Glutaric acid-(4-benzyl-4-dimethylamino-cyclohexyl)-amide [2-(4-fluoro-phenyl)-ethyl]-amide; Glutaric acid-(4-benzyl-4-dimethylamino-cyclohexyl)-amide [1-(2,6-dichloro-benzyl)-pyrrolidin-3-yl]-amide; N-[4-(4-chloro-benzyl)-4-dimethylamino-cyclohexyl]-4-(1,4-dioxa-8-aza-spiro[4.5]dec-8-yl)-4-oxo-butyramide; N-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-4-oxo-4-thiomorpholin-4-yl-butyramide; 4-(4-benzoyl-piperidin-1-yl)-N-[4-dimethylamino-4-(3-methyl-benzyl)-cyclohexyl]-4-oxo-butyramide; N-[4-(4-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-(2,4-dimethoxy-benzyl)-succinamide; N-[4-dimethylamino-4-(3-methyl-benzyl)-cyclohexyl]-N′-(1,2,3,4-tetrahydro-naphthalen-1-yl)-succinamide; N-[4-(4-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-ethyl-N′-pyridin-4-ylmethyl-succinamide; N-[2-(3,4-dimethoxy-phenyl)-ethyl]-N′-[4-dimethylamino-4-(3-methyl-benzyl)-cyclohexyl]-N-methyl-succinamide; N-[4-(4-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-methyl-N′-pyridin-3-ylmethyl-succinamide; N-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-pyridin-2-ylmethyl-succinamide; N-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-(2-methyl-benzyl)-succinamide; N-[4-dimethylamino-4-(3-methyl-benzyl)-cyclohexyl]-N′-(4-methoxy-phenyl)-succinamide; N-[4-dimethylamino-4-(3-methyl-benzyl)-cyclohexyl]-N′-indan-2-yl-succinamide; N-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-(1-methyl-3-phenyl-propyl)-succinamide; N-(2-chloro-6-methyl-benzyl)-N′-[4-dimethylamino-4-(3-methyl-benzyl)-cyclohexyl]-succinamide; N-[4-dimethylamino-4-(4-methyl-benzyl)-cyclohexyl]-4-[4-(4-methoxy-phenyl)-piperazin-1-yl]-4-oxo-butyramide; N-[4-dimethylamino-4-(4-methyl-benzyl)-cyclohexyl]-N′-[2-(4-fluoro-phenyl)-ethyl]-succinamide; Glutaric acid-(4-benzyl-4-dimethylamino-cyclohexyl)-amide 4-dimethylamino-benzylamide; N-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-(3,5-dichloro-benzyl)-succinamide; N-[4-(4-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-(1-methyl-3-phenyl-propyl)-succinamide; 4-{3-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexylcarbamoyl]-propionyl}-piperazin-1-carboxylic acid ethylester; N-[4-dimethylamino-4-(3-methyl-benzyl)-cyclohexyl]-N′-(4-methoxy-benzyl)-succinamide; N-[4-(4-chloro-benzyl)-4-dimethylamino-cyclohexyl]-4-(2,6-dimethyl-morpholin-4-y1)-4-oxo-butyramide; N-[4-dimethylamino-4-(4-methyl-benzyl)-cyclohexyl]-4-oxo-4-(4-phenyl-3,6-dihydro-2H-pyridin-1-yl)-butyramide; N-[4-(4-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-[2-(3-fluoro-phenyl)-ethyl]-succinamide; 4-[4-(4-allyloxy-benzyp-piperazin-1-yl]-N-[4-dimethylamino-4-(3-methyl-benzyl)-cyclohexyl]-4-oxo-butyramide; Glutaric acid-(4-benzyl-4-dimethylamino-cyclohexyl)-amide [2-(5-bromo-2-methoxy-phenyl)-ethyl]-amide; 5-[4-(3-methoxy-phenyl)-piperazin-1-yl]-5-oxo-valeric acid (4-benzyl-4-dimethylamino-cyclohexyl)-amide; N-[4-(3-chloro-benzyl)- 4- dimethylamino-cyclohexyl]- 4-(4-methyl-piperidin-1-yl)-4-oxo-butyramide; (4-{3-[4-(4-chloro-benzyl)-4-dimethylamino-cyclohexylcarbamoyl]-propionylamino}-benzyl)-phosphonic acid diethylester; N-[4-dimethylamino-4-(4-methyl-benzyl)-cyclohexyl]-4-oxo-4-(4-o-tolyl-piperazin-1-y1)-butyramide; N-[4-dimethylamino-4-(3-methyl-benzyl)-cyclohexyl]-N′-[2-(3-fluoro-phenyl)-ethyl]-succinamide; 4-[4-(4-chloro-phenyl)-piperazin-1-yl]-N-[4-dimethylamino-4-(4-methyl-benzyl)-cyclohexyl]-4-oxo-butyramide; N-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-[1-(4-fluoro-phenyl)-ethyl]-succinamide; N-[4-(4-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-[1-(4-trifluoromethyl-benzyl)-pyrrolidin-3-yl]-succinamide; N-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-[2-(1H-indol-3-yl)-ethyl]-succinamide; N-[4-(4-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-indan-5-yl-succinamide; N-(4-benzyloxy-phenyl)-N′-[4-dimethylamino-4-(4-methyl-benzyl)-cyclohexyl]-succinamide; 2-{3-[4-dimethylamino-4-(3-methyl-benzyl)-cyclohexylcarbamoyl]-propionylamino}-3-methyl-valeric acid tert-butyl ester; 4-(4-benzyl-piperidin-1-yl)-N-[4-dimethylamino-4-(3-methyl-benzyl)-cyclohexyl]-4-oxo-butyramide; N-[4-(4-chloro-benzyl)-4-dimethylamino-cyclohexyl]-4-[4-(4-fluoro-phenyl)-3,6-dihydro-2H-pyridin-1-yl]-4-oxo-butyramide; N-[4-dimethylamino-4-(4-methyl-benzyl)-cyclohexyl]-N′-(1,2-dimethyl-propyl)-succinamide; N-[4-dimethylamino-4-(3-methyl-benzyl)-cyclohexyl]-4-(8-fluoro-1,3,4,5-tetrahydro-pyrido[4,3-b]indo1-2-yl)-4-oxo-butyramide, 4-[4-(3-chloro-benzoyl)-piperazin-1-yl]-N-[4-dimethylamino-4-(3-methyl-benzyl)-cyclohexyl]-4-oxo-butyramide; N-[4-(4-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-(4-methoxy-phenyl)-succinamide; 5-[4-(2,6-dichloro-benzyl)-piperazin-1-yl]-5-oxo-valeric acid (4-benzyl-4-dimethylamino-cyclohexyl)-amide; N-[4-dimethylamino-4-(3-methyl-benzyl)-cyclohexyl]-N′-[2-(1H-indol-3-yl)-ethyl]-N′-methyl-succinamide; N-[4-dimethylamino-4-(3-methyl-benzyl)-cyclohexyl]-N′-[1-(4-fluoro-phenyl)-ethyl]-succinamide; 4-[4-(4-chloro-phenyl)-piperazin-1-yl]-N-[4-dimethylamino-4-(3-methyl-benzyl)-cyclohexyl]-4-oxo-butyramide; N-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-4-oxo-4-(4-oxo-1-phenyl-1,3,8-triaza-spiro[4.5]dec-8-yl)-butyramide; N-benzyl-N′-[4-dimethylamino-4-(3-methyl-benzyl)-cyclohexyl]-N-methyl-succinamide; N-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-(3,5-difluoro-benzyl)-succinamide; N-[4-dimethylamino-4-(3-methyl-benzyl)-cyclohexyl]-N′-[2-(4-fluoro-phenyl)-ethyl]-succinamide; N-[4-dimethylamino-4-(3-methyl-benzyl)-cyclohexyl]-N′-[2-(1H-indo1-3-yl)-ethyl]-succinamide; N-(2-benzylsulphanyl-ethyl)-N′-[4-dimethylamino-4-(3-methyl-benzyl)-cyclohexyl]-succinamide; N-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-(2,4-difluoro-benzyl)-succinamide; N-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-phenethyl-succinamide; N-[4-dimethylamino-4-(3-methyl-benzyl)-cyclohexyl]-N′-(1-naphthalen-2-yl-ethyl)-succinamide; N-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-(1-methoxymethyl-2-phenyl-ethyl)-succinamide; N-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-(3,4-dichloro-benzyl)-succinamide; N-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-furan-2-ylmethyl-succinamide; N-[4-dimethylamino-4-(4-methyl-benzyl)-cyclohexyl]-N′-(1,2,3,4-tetrahydro-naphthalen-1 -yl)-succinamide; N-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-(4-fluoro-benzyl)-succinamide; N-[4-dimethylamino-4-(3-methyl-be nzyl)-cyclohexyl]-N′-indan-1-yl-succinamide; N-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-4-(3,5-dimethyl-piperidin-1-yl )-4-oxo-butyramide; N-[4-dimethylamino-4-(3-methyl-benzyl)-cyclohexyl]-N′-phenethyl-succinamide; N-[4-dimethylamino-4-(4-methyl-benzyl)-cyclohexyl]-N′-phenethyl-succinamide; N-(2-benzylsulphanyl-ethyl)-N′-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-succinamide; N-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-(2,5-dichloro-benzyl)-succinamide; 4-[4-(3-chloro-benzoyl)-piperazin-1-yl]-N-[4-(4-chloro-benzyl)-4-dimethylamino-cyclohexyl]-4-oxo-butyramide; N-[4-(4-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-(1-phenyl-propyl)-succinamide; N-(4-bromo-2-fluoro-benzyl)-N′-[4-dimethylamino-4-(3-methyl-benzyl)-cyclohexyl]-succinamide; N-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-methyl-N′-pyridin-3-ylmethyl-succinamide; N-[4-dimethylamino-4-(4-methyl-benzyl)-cyclohexyl]-N′-(2-ethoxy-benzyl)-succinamide; N-[4-dimethylamino-4-(3-methyl-benzyl)-cyclohhexyl]-N′-[2-(5-methoxy-1H-indol-3-yl)-ethyl]-succinamide; N-(4-sec-butyl-phenyl)-N′-[4-(4-chloro-benzyl)-4-dimethylamino-cyclohexyl]-succinamide; 5-oxo-5-(4-phenyl-3,6-dihydro-2H-pyridin-1-yl)-valeric acid (4-benzyl-4-dimethylamino-cyclohexyl)-amide; 5-oxo-5-(4-phenyl-3,6-dihydro-2H-pyridin-1-yl)-valeric acid (4-benzyl-4-dimethylamino-cyclohexyl)-amide; N-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-[2-(3-fluoro-phenyl)-ethyl]-succinamide; N-(3-bromo-benzyl)-N′-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-succinamide; N-(4-bromo-2-fluoro-benzyl)-N′-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-succinamide; N-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-(1-phenyl-propyl)-succinamide; N-[4-dimethylamino-4-(3-methyl-benzyl)-cyclohexyl]-N′-(4-fluoro-2-trifluoromethyl-benzyl)-succinamide; N-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-indan-2-yl-succinhmide; N-[4-dimethylamino-4-(3-methyl-benzyl)-cyclohexyl]-4-oxo-4-(4-phenyl-3,6-dihydro-2H-pyridin-1-yl)-butyramide; N-[4-(4-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-[2-(2-fluoro-phenyl)-ethyl]-succinamide; N-[4-dimethylamino-4-(4-methyl-benzyl)-cyclohexyl]-N′-[2-(2-fluoro-phenyl)-ethyl]-succinamide; Glutaric acid-(4-benzyl-4-dimethylamino-cyclohexyl)-amide [2-(2-fluoro-phenyl)-ethyl]-amide; N-[2-(2-chloro-phenyl)-ethyl]-N′-[4-dimethylamino-4-(4-methyl-benzyl)-cycloheXyl]-succinamide; N-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-(3,4-difluoro-benzyl)-succinamide; N-benzyl-N-(2-cyano-ethyl)-N′-[4-dimethylamino-4-(4-methyl-benzyl)-cyclohexyl]-succinamide; N-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-(3-methyl-benzyl)-succinamide; N-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-(4-fluoro-3-trifluoromethyl-benzyl)-succinamide; N-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-[2-(2-chloro-phenyl)-ethyl]-succinamide; N-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-[2-(4-chloro-phenyl)-ethyl]-succinamide; N-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-[2-(2,4-dichloro-phenyl)-ethyl]-succinamide; N-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-indan-1-yl-succinamide; N-[4-(4-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-indan-1-yl-succinamide; N-[2-(4-chloro-phenyl)-propyl]-N′-[4-dimethylamino-4-(3-methyl-benzyl)-cyclohexyl]-succinamide; N-(3-bromo-benzyl)-N′-[4-(4-chloro-benzyl)-4-dimethylamino-cyclohexyl]-succinamide; N-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-(3-phenyl-propyl)-succinamide; N-[4-dimethylamino-4-(4-methyl-benzyl)-cyclohexyl]-N′-(2-p-tolyl-ethyl)-succinamide; N-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-(2-thiophen-2-yl-ethyl)-succinamide; Glutaric acid-(4-benzyl-4-dimethylamino-cyclohexyl)-amide [2-(4-chloro-phenyl)-propyl]-amide; N-benzyl-N′-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N-methyl-succinamide; N-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-[2-(3-chloro-phenyl)-ethyl]-succinamide; Glutaric acid-(4-benzyl-4-dimethylamino-cyclohexyl)-amide [2-(2-ethoxy-phenyl)-ethyl]-amide; Glutaric acid-(4-benzyl-4-dimethylamino-cyclohexyl)-amide phenethyl-amide; Glutaric acid-(4-benzyl-4-dimethylamino-cyclohexyl)-amide [2-(3-chloro-phenyl)-ethyl]amide; N-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-[1-(3-methoxy-phenyl)-ethyl]-succinamide; Glutaric acid-(4-benzyl-4-dimethylamino-cyclohexyl)-amide (1,3-dimethyl-butyl)-amide; N-benzyl-N′-[4-dimethylamino-4-(3-methyl-benzyl)-cyclohexyl]-N-ethyl-succinamide; N-(4-chloro-benzyl)-N′-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-succinamide; N-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-[2-(2-fluoro-phenyl)-ethyl]-succinamide; N-[4-dimethylamino-4-(3-methyl-benzyl)-cyclohexyl]-N′-(2-fluoro-benzyl)-succinamide; N-[2-(4-chloro-phenyl)-ethyl]-N′-[4-dimethylamino-4-(3-methyl-benzyl)-cyclohexyl]-succinamide; N-[2-(2-chloro-phenyl)-ethyl]-N′-[4-dimethylamino-4-(3-methyl-benzyl)-cyclohexyl]-succinamide; N-[2-(3-chloro-phenyl)-ethyl]-N′-[4-dimethylamino-4-(3-methyl-benzyl)-cyclohexyl]-succinamide; N-benzyl-N′-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N-(2-cyano-ethyl)-succinamide; N-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-(3-chloro-4-fluoro-benzyl)-succinamide; N-[4-dimethylamino-4-(3-methyl-benzyl)-cyclohexyl]-N′-(2-trifluoromethyl-benzyl)-succinamide; N-[2-(2,4-dichloro-phenyl)-ethyl]-N′-[4-dimethylamino-4-(3-methyl-benzyl)-cyclohexyl]-succinamide; N-benzyl-N′-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N-ethyl-succinamide; N-[2-(4-chloro-phenyl)-ethyl]-N′-[4-dimethylamino-4-(4-methyl-benzyl)-cyclohexyl]-succinamide; 5-oxo-5-(4-o-tolyl-piperazin-1-yl)-valeric acid (4-benzyl-4-dimethylamino-cyclohexyl)-amide; N-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-[3-(methyl-phenyl-amino)-propyl]-succinamide; N-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-4-[4-(5-chloro-2-methyl-phenyl)-piperazin-1-yl]-4-oxo-butyramide; N-[4-dimethylamino-4-(3-methyl-benzyl)-cyclohexyl]-N′-[2-(2-ethoxy-phenyl)-ethyl]-succinamide; 4-[4-(4-chloro-benzoyl)-piperidin-1-yl]-N-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-4-oxo-butyramide; N-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-[2-(2-ethoxy-phenyl)-ethyl]-succinamide; N-[2-(2,6-dichloro-phenyl)-ethyl]-N′-[4-dimethylamino-4-(3-methyl-benzyl)-cyclohexyl]-succinamide; N-benzhydryl-N′-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-succinamide; N-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-cyclooctyl-succinamide; N-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-[2-(4-phenoxy-phenyl)-ethyl]-succinamide; N-[4-dimethylamino-4-(3-methyl-benzyl)-cyclohexyl]-N′-(2,3-dimethyl-benzyl)-succinamide; 4-[4-(5-chloro-2-methyl-phenyl)-piperazin-1-yl]-N-[4-dimethylamino-4-(3-methyl-benzyl)-cyclohexyl]-4-oxo-butyramide; 4-[4-(4-chloro-benzoyl)-piperidin-1-yl]-N-[4-dimethylamino-4-(3-methyl-benzyl)-cyclohexyl]-4-oxo-butyramide; N-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-(1,2,3,4-tetrahydro-naphthalen-1-yl)-succinamide; N-(2-chloro-benzyl)-N′-[4-dimethylamino-4-(3-methyl-benzyl)-cyclohexyl]-succinamide; N-(2-chloro-benzyl)-N′-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-succinamide; N-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-(3-fluoro-5-trifluoromethyl-benzyl)-succinamide; N-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-(1-p-tolyl-ethyl)-succinamide; N-[2-(2,6-dichloro-benzylsulphanyl)-ethyl]-N′-[4-dimethylamino-4-(4-methyl-benzyl)-cyclohexyl]-succinamide; N-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-[2-(2,6-dichloro-benzylsulphanyl)-ethyl]-succinamide; N-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-[2-(3-trifluoromethyl-phenyl)-ethyl]-succinamide; N-[2-(3,4-dichloro-phenyl)-ethyl]-N′-[4-dimethylamino-4-(3-methyl-benzyl)-cyclohexyl]-succinamide; N-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-4-[4-(2-fluoro-phenyl)-piperazin-1-yl]-4-oxo-butyramide; 5-[4-(2,4-dimethoxy-phenyl)-piperazin-1-yl]-5-oxo-valeric acid (4-benzyl-4-dimethylamino-cyclohexyl)-amide; N-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-(1-naphthalen-1-yl-ethyl)-succinamide; N-[4-dimethylamino-4-(3-methyl-benzyl)-cyclohexyl]-N′-(1-naphthalen-1-yl-ethyl)-succinamide; N-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-(2-fluoro-benzyl)-N′-furan-2-ylmethyl-succinamide; N-[4-dimethylamino-4-(3-methyl-benzyl)-cyclohexyl]-N′-(2-fluoro-benzyl)-N′-furan-2-ylmethyl-succinamide; N-[4-(3-chloro-benzyl)-4-dimethylamino-cyclohexyl]-N′-(2,5-dimethoxy-benzyl)-N′-furan-2-ylmethyl-succinamide; N-(4-azepan-1-yl-4-benzyl-cyclohexyl)-4-(2,3-dihydro-indo1-1-yl)-4-oxo-butyramide; 4-(2,3-dihydro-indol-1-yl)-N-[4-dimethylamino-4-(3-fluoro-phenyl)-cyclohexyl]-4-oxo-butyramide; N-(4-benzyl-4-morpholin-4-yl-cyclohexyl)-N′-(2-chloro-6-methyl-benzyl)-succinamide; N-(4-benzyl-4-morpholin-4-yl-cyclohexyl)-N′-[2-(3-methoxy-phenyl)-ethyl]-succinamide; N-(4-benzyl-4-morpholin-4-yl-cyclohexyl)-N′-(3-methyl-benzyl)-succinamide; N-(4-benzyl-4-morpholin-4-yl-cyclohexyl)-N′-(4-bromo-2-fluoro-benzyl)-succinamide; N-(4-benzyl-4-morpholin-4-yl-cyclohexyl)-N′-pyridin-4-ylmethyl-succinamide; N-(4-benzyl-4-morpholin-4-yl-cyclohexyl)-N′-indan-1-yl-succinamide; N-(4-benzyl-4-morpholin-4-yl-cyclohexyl)-N′-(2,4-dimethoxy-benzyl)-succinamide; N-(4-benzyl-4-morpholin-4-yl-cyclohexyl)-N′-thiophen-2-ylmethyl-succinamide; N-adamantan-1-ylmethyl-N′-(4-benzyl-4-morpholin-4-yl-cyclohexyl)-succinamide; N-(4-benzyl-4-morpholin-4-yl-cyclohexyl)-N′-(2,5-difluoro-benzyl)-succinamide; N-(4-benzyl-4-morpholin-4-yl-cyclohexyl)-N′-(4-tert-butyl-phenyl)-succinamide; N-(4-benzyl-4-morpholin-4-yl-cyclohexyl)-N′-(3,5-bis-trifluoromethyl-benzyl)-succinamide; N-(4-benzyl-4-morpholin-4-yl-cyclohexyl)-N′-[2-(2-ethoxy-phenyl)-ethyl]-succinamide; N-(4-benzyl-4-morpholin-4-yl-cyclohexyl)-N′-(3-methoxy-propyl)-succinamide; N-(4-benzyl-4-morpholin-4-yl-cyclohexyl)-N′-(2-morpholin-4-yl-ethyl)-succinamide; N-(4-benzyl-4-morpholin-4-yl-cyclohexyl)-N′-(2,5-dichloro-benzyl)-succinamide; N-(4-benzyl-4-morpholin-4-yl-cyclohexyl)-N′-[1-(2-benzyloxy-benzyl)-pyrrolidin-3-yl]-N′-methyl-succinamide; N-(4-benzyl-4-morpholin-4-yl-cyclohexyl)-4-oxo-4-(2-pyrrolidin-1-ylmethyl-pyrrolidin-1-yl)-butyramide; N-(4-benzyl-4-morpholin-4-yl-cyclohexyl)-4-morpholin-4-yl-4-oxo-butyramide; N-(4-benzyl-4-morpholin-4-yl-cyclohexyl)-N′-(3-dimethylamino-propyl)-N′-methyl-succinamide; N-(4-benzyl-4-morpholin-4-yl-cyclohexyl)-N′-(2-phenyl-cyclopropyl)-succinamide; N-(4-benzyl-4-morpholin-4-yl-cyclohexyl)-N′-naphthalen-1-ylmethyl-succinamide; N-(4-benzyl-4-morpholin-4-yl-cyclohexyl)-4-(4-methyl-[1,4]diazepan-1-yl)-4-oxo-butyramide; N-(4-benzyl-4-morpholin-4-yl-cyclohexyl)-4-(4-hydroxy-piperidin-1-yl)-4-oxo-butyramide; N-(4-benzyl-4-morpholin-4-yl-cyclohexyl)-N′-[2-(7-methyl-1H-indol-3-yl)-ethyl]-succinamide; N-(4-benzyl-4-morpholin-4-yl-cyclohexyl)-N′-[2-(5-methoxy-1H-indo1-3-yl)-ethyl]-succinamide; N-(4-benzyl-4-morpholin-4-yl-cyclohexyl)-4-oxo-4-(4-quinolin-2-ylmethyl-piperazin-1-yl)-butyramide; N-(4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-4-oxo-4-[4-(5-trifluoromethyl-pyridin-2-yl)-piperazin-1-yl]-butyramide; Glutaric acid-(1-adamantan-1-yl-ethyl)-amide (4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-amide; N-[2-(2,6-dichloro-phenyl)-ethyl]-N′-(4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-succinamide; N-(4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-N′-(1-methyl-3-phenyl-propyl)-succinamide; N-benzyl-N′-(4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-N-ethyl-succinamide; N-[2-(4-bromo-phenyl)-ethyl]-N′-(4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-succinamide; 4-[4-(4-chloro-benzoyl)-piperidin-1-yl]-N-(4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-4-oxo-butyramide; Glutaric acid-[1-(2,6-dichloro-benzyl)-pyrrolidin-3-yl]-amide (4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-amide; Glutaric acid-(4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-amide (3-phenyl-propyl)-amide; N-(4-dimethylamino-4-phenyl-cyclohexyl)-N′-pentyl-succinamide; 3-(4-chloro-phenyl)-2-[4-(4-dimethylamino-4-thiophen-2-yl-cyclohexylcarbamoyl)-butyrylamino]-propanoic acid ethylester; Glutaric acid-(4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-amide indan-1-ylamide; N-adamantan-1-ylmethyl-N′-(4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-succinamide; 5-(4-benzofuran-2-ylmethyl-piperazin-1-yl)-5-oxo-valeric acid (4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-amide; 4-[4-(4-tert-butyl-benzyl)-piperazin-1-yl]-N-(4-dimethylamino-4-phenyl-cyclohexyl)-4-oxo-butyramide; Glutaric acid-(4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-amide [2-(1H-indo1-3-y1)-ethyl]-amide; N-(4-dimethylamino-4-phenyl-cyclohexyl)-4-[4-hydroxy-4-(3-trifluoromethyl-phenyl)-piperidin-1-yl]-4-oxo-butyramide; 5-(3,4-dihydro-1H-isoquinolin-2-yl)-5-oxo-valeric acid (4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-amide; 4-(4-benzyl-pip eridin-1-yl)-N-(4-dimethylamino-4-phenyl-cyclohexyl)-4-oxo-butyramide; {[4-(4-dimethylamino-4-thiophen-2-yl-cyclohexylcarbamoyl)-butyryl]-methyl-amino}-acetic acid benzylester; N-benzyl-N′-(4-dimethylamino-4-phenyl-cyclohexyl)-N-phenethyl-succinamide; Glutaric acid-(4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-amide 3-trifluoromethoxy-benzylamide; Glutaric acid-(4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-amide ethyl-(2-methyl-allyl)-amide; N,N-bis-(2-cyano-ethyl)-N′-(4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-succinamide; Glutaric acid-benzyl-methyl-amide (4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-amide; Glutaric acid-(2-benzyloxy-cyclopentyl)-amide (4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-amide; Glutaric acid-(4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-amide 4-trifluoromethyl-benzylamide; N-(4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-N′-[2-(4-phenoxy-phenyl)-ethyl]-succinamide; Glutaric acid-(4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-amide (3,3-diphenyl-propyl)-amide; 4-(4-benzyl-piperidin-1-yl)-N-(4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-4-oxo-butyramide; N-(4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-4-[4-hydroxy-4-(3-trifluoromethyl-phenyl)-piperidin-1-yl]-4-oxo-butyramide; Glutaric acid-(4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-amide 4-fluoro-2-trifluoromethyl-benzylamide; N-(4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-N′-pentyl-succinamide; 5-[4-(2-methoxy-naphthalen-1-ylmethyl)-piperazin-1-yl]-5-oxo-valeric acid (4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-amide; N-(4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-N′-(2-ethoxy-benzyl)-N′-furan-2-ylmethyl-succinamide; Glutaric acid-(4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-amide (2-phenyl-cyclopropyl)-amide; N-[2-(3,4-dichloro-phenyl)-ethyl]-N′-(4-dimethylamino-4-phenyl-cyclohexyl)-succinamide; N-adamantan-1-ylmethyl-N′-(4-dimethylamino-4-phenyl-cyclohexyl)-succinamide; 5-[4-(4-fluoro-phenyl)-3,6-dihydro-2H-pyridin-1-yl]-5-oxo-valeric acid (4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-amide; 2-[4-(4-dimethylamino-4-thiophen-2-yl-cyclohexylcarbamoyl)-butyrylamino]-4-methyl-valeric acid benzyl ester; {4-[4-(4-dimethylamino-4-thiophen-2-yl-cyclohexylcarbamoyl)-butyrylamino]-phenyl}-carbamic acid-tert-butylester; Glutaric acid-(4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-amide [2-(3-methoxy-phenyl)-ethyl]-amide; Glutaric acid-benzyl-ethyl-amide (4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-amide; Glutaric acid-3-chloro-benzylamide (4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-amide; Glutaric acid-(4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-amide (4-methyl-cyclohexyl)-amide; N-(4-dimethylamino-4-phenyl-cyclohexyl)-N′-[2-(1H-indol-3-yl)-ethyl]-N′-methyl-succinamide; Glutaric acid-2,5-dichloro-benzylamide (4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-amide; Glutaric acid-(4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-amide [2-(3-fluoro-phenyl)-ethyl]-amide; N-(4-dimethylamino-4-phenyl-cyclohexyl)-N′-[2-(4-methoxy-phenoxy)-ethyl]-succinamide; N-(4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-N′-[2-(ethyl-m-tolyl-amino)-ethyl]-succinamide; Glutaric acid-(4-benzyloxy-phenyl)-amide (4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-amide; Glutaric acid-(4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-amide [2-(4-fluoro-phenyl)-ethyl]-amide; Glutaric acid-[2-(4-bromo-phenyl)-ethyl]-amide (4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-amide; N-(4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-N′-(4-phenoxy-phenyl)-succinamide; N-(4-dimethylamino-4-phenyl-cyclohexyl)-N′-[2-(3-trifluoromethyl-phenyl)-ethyl]-succinamide; Glutaric acid-[2-(4-chloro-phenyl)-propyl]-amide (4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-amide; N-(4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-N′-[2-(1H-indol-3-yl)-ethyl]-N′-methyl-succinamide; N-(4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-N′-[2-(4-methoxy-phenoxy)-ethyl]-succinamide; Glutaric acid-(4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-amide (3-phenoxy-phenyl)-amide; N-(4-dimethylamino-4-phenyl-cyclohexyl)-N′-[2-(ethyl-m-tolyl-amino)-ethyl]-succinamide; Glutaric acid-[2-(5-bromo-2-methoxy-phenyl)-ethyl]-amide (4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-amide; N-(4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-N′-[2-(3-trifluoromethyl-phenyl)-ethyl]-succinamide; Glutaric acid-(4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-amide (1-methyl-3-phenyl-propyl)-amide; N-[2-(2,6-dichloro-benzylsulphanyl)-ethyl]-N′-(4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-succinamide; Glutaric acid-(4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-amide (2,2-diphenyl-propyl)-amide; N-(4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-N′-[3-(methyl-phenyl-amino)-propyl]-succinamide; N-(1-biphenyl-4-ylmethyl-pyrrolidin-3-yl)-N′-(4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-N-methyl-succinamide; Glutaric acid-[4-(cyano-phenyl-methyl)-phenyl]-amide (4-dimethylamino-4-thiophen-2-ylcyclohexyl)-amide; Glutaric acid-(4-tert-butyl-cyclohexyl)-amide (4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-amide; Glutaric acid-(4-sec-butyl-phenyl)-amide (4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-amide; Glutaric acid-(4-butyl-phenyl)-amide (4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-amide; N-(2-benzylsulphanyl-ethyl)-N′-(4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-succinamide; N-(4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-N′-(2-phenoxy-ethyl)-succinamide; Glutaric acid-(4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-amide (naphthalen-1-ylmethyp-amide; Glutaric acid-3-bromo-benzylamide (4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-amide; N-(4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-N′-(3-phenyl-propyl)-succinamide; N-[2-(3-chloro-phenyl)-ethyl]-N′-(4-dimethylamino-4-phenyl-cyclohexyl)-succinamide; 2-[3-(4-dimethylamino-4-thiophen-2-yl-cyclohexylcarbamoyl)-propionylamino]-; propanoic acid benzylester; N-[2-(2-chloro-phenyl)-ethyl]-N′-(4-dimethylamino-4-phenyl-cyclohexyl)-succinamide; N-(4-dimethylamino-4-phenyl-cyclohexyl)-N′-[2-(3-fluoro-phenyl)-ethyl]-succinamide; Glutaric acid-(4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-amide (2-thiophen-2-yl-ethyl)-amide; Glutaric acid-(4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-amide [2-(4-phenoxy-phenyl)-ethyl]-amide; N-[2-(4-chloro-phenyl)-ethyl]-N′-(4-dimethylamino-4-phenyl-cyclohexyl)-succinamide; N-[2-(3-chloro-phenyl)-ethyl]-N′-(4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-succinamide; N-benzyl-N′-(4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-N-ethyl-succinamide; Glutaric acid-[1-(2,6-dichloro-benzyl)-pyrrolidin-3-yl]-amide (4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-amide; Glutaric acid-(4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-amide (3-phenyl-propyl)-amide; Glutaric acid-(4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-amide [2-(1H-indo1-3-yl)-ethyl]-amide; 5-(3,4-dihydro-1H-isoquinolin-2-yl)-5-oxo-valeric acid (4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-amide; {[4-(4-dimethylamino-4-thiophen-2-yl-cyclohexylcarbamoyl)-butyryl]-methyl-amino}-acetic acid benzylester; N-(4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-N′-[2-(4-phenoxy-phenyl)-ethyl]-succinamide; Glutaric acid-(4-dimethylamino-4-thiophen-2-yl-cyclohexyl)-amide (2-phenyl-cyclopropyl)-amide; N-[4-(3-chlorobenzyl)-4-dimethylaminocyclohexyl]-N′-furan-2-ylmethylsuccinic acid amide hydrochloride, non-polar diastereoisomer; N-[4-(3-chlorobenzyl)-4-dimethylaminocyclohexyl]-N′-furan-2-ylmethylsuccinic acid amide hydrochloride, polar diastereoisomer; Glutaric acid (4-benzyl-4-dimethylaminocyclohexyl)amide [2-(2-fluorophenyl)ethyl]amide hydrochloride, non-polar diastereoisomer; Glutaric acid (4-benzyl-4-dimethylaminocyclohexyl)amide [2-(2-fluorophenyl)ethyl]amide hydrochloride, polar diastereoisomer; N-[4-(3-chlorobenzyl)-4-dimethylaminocyclohexyl]-N′-[2-(4-chlorophenyl)ethyl]-succinic acid amide hydrochloride, non-polar diastereoisomer; N-[4-(3-chlorobenzyl)-4-dimethylaminocyclohexyl]-N′-[2-(4-chlorophenyl)ethyl]-succinic acid amide hydrochloride, polar diastereoisomer; and Glutaric acid (4-benzyl-4-dimethylaminocyclohexyl)amide [2-(4-chlorophenyl)ethyl]amide hydrochloride, non-polar diastereoisomer.
 18. A process for preparing a cyclohexyl-1,4-diamine compound according to claim 1, comprising the steps of: linking a cyclohexane-1,4-diamine compound to a primary or secondary amine via an anhydride, open-chain dicarboxylic acid or an activated analog thereof.
 19. The method of claim 18, wherein said activated analog is an acid halide.
 20. A process for preparing a cyclohexyl-1,4-diamine compound according to claim 1, comprising the steps of: reacting one or more coupling agents to link an anhydride, open-chain dicarboxylic acid or an activated analog thereof with a primary or secondary amine and linking a substituted cyclohexane-1,4-diamine thereto.
 21. The method of claim 20, wherein said activated analog is an acid halide.
 22. A pharmaceutical formulation comprising at least one cyclohexyl-1,4-diamine compound according to claim 1 and one or more physiologically acceptable auxiliary substances.
 23. A method of producing a pharmaceutical formulation comprising the steps of combining a pharmaceutically effective amount of a cyclohexyl-1,4-diamine compound according to claim 1 and one or more physiologically acceptable auxiliary substances.
 24. A method of treating pain in a mammal, said method comprising administering to said mammal an effective amount of a compound according to claim
 1. 25. The method of claim 24, wherein said pain is acute, neuropathic or chronic pain.
 26. A method of treating a condition selected from the group consisting of anxiety, stress and stress-related syndromes, depression, epilepsy, withdrawal symptoms, alcohol abuse or dependency, drug abuse or dependency, medicine abuse or dependency, sexual dysfunction, hypotension, hypertension, tinnitus, pruritus, migraine, deficient intestinal motility, impaired nutrient absorption, anorexia, obesity, diarrhea, cachexia, urinary incontinence, or providing a muscle relaxant, nootropic, anti-convulsive or anaesthetic or for co-administration in treatment with an opioid analgesic or anaesthetic, for diuresis or anti-natriuresis, anxiolysis, for the treatment of withdrawal symptoms or for reducing opioid addiction potential, said method comprising administering to a subject in need thereof a pharmaceutically effective amount of a compound according to claim
 1. 27. A cyclohexyl-1,4-diamine compound corresponding to formula I,

wherein n represents 1, 2, 3, 4 or 5 R¹ and R² independently of one another represent H; saturated or unsaturated, branched or unbranched, singly or multiply substituted or unsubstituted C₁₋₅ alkyl; singly or multiply substituted or unsubstituted C₃₋₈ cycloalkyl; or singly or multiply substituted or unsubstituted aryl, C₃₋₈ cycloalkyl or heteroaryl bound by C₁₋₃ alkyl; or R¹and R² together form a ring and represent CH₂CH₂OCH₂CH₂, CH₂CH₂NR¹⁰CH₂CH₂ or (CH2)₃₋₆, wherein R¹⁰ represents H; saturated or unsaturated, branched or unbranched, singly or multiply substituted or unsubstituted C₁₋₅ alkyl singly or multiply substituted or unsubstituted C₃₋₈ cycloalkyl; singly or multiply substituted or unsubstituted aryl or heteroaryl; or singly or multiply substituted or unsubstituted aryl, C₃₋₈ cycloalkyl or heteroaryl bound by C₁₋₃ alkyl; substituted or unsubstituted C(O)phenyl, C(O)heteroaryl, C(O)C₁₋₅ alkyl; R³ represents saturated or unsaturated, branched or unbranched, singly or multiply substituted or unsubstituted C₁₋₅ alkyl; singly or multiply substituted or unsubstituted C₃₋₈ cycloalkyl; unsubstituted or singly or multiply substituted aryl or heteroaryl; unsubstituted or singly or multiply substituted aryl, heteroaryl or C₃₋₈ cycloalkyl bound by a C₁₋₃ alkyl group; R⁴ represents —(CR⁶R⁷)_(p)R⁸, wherein p represents 0, 1, 2, 3 or 4; R⁶ represents H or saturated or unsaturated, branched or unbranched, unsubstituted or singly or multiply substituted C₁₋₅ alkyl; R⁷ represents H, saturated or unsaturated, branched or unbranched, unsubstituted or singly or multiply substituted C₁₋₅ alkyl or COORS⁹; or R⁶ and R⁷ together form a ring and represent (CH₂)_(k)CHR⁸(CH₂)_(m), where k =1, 2, or 3 and m =1 or 2; R⁸ represents respectively saturated or unsaturated, branched or unbranched, unsubstituted or singly or multiply substituted C₁₋₆ alkyl; unsubstituted or singly or multiply substituted C₃₋₈ cycloalkyl, aryl or heteroaryl; R⁹ represents H or C₁₋₅ alkyl; R⁵ represents H or —(CH₂)_(l)R⁸, wherein l represents 1, 2 or 3 or R⁵ and R⁴ together form a ring and represent CH₂CHR¹⁴CHR¹⁴CH₂, CH₂CH₂SCH₂CH₂ CH₂CH₂NR¹¹CH₂CH₂, (CR¹²R¹³)₃₋₆ or

wherein R¹¹ represents H; saturated or unsaturated, branched or unbranched, singly or multiply substituted or unsubstituted C₁₋₅ alkyl; saturated or unsaturated, singly or multiply substituted or unsubstituted C₃₋₈ cycloalkyl; singly or multiply substituted or unsubstituted aryl or heteroaryl; or singly or multiply substituted or unsubstituted aryl, C₃₋₈ cycloalkyl or heteroaryl bound by C₁₋₃ alkyl; R¹² represents H; saturated or unsaturated, branched or unbranched, singly or multiply substituted or unsubstituted C₁₋₅ alkyl; OH; unsubstituted or singly or multiply substituted C(O)phenyl; singly or multiply substituted or unsubstituted C₃₋₈ cycloalkyl; respectively singly or multiply substituted or unsubstituted aryl or heteroaryl; or singly or multiply substituted or unsubstituted aryl, C₃₋₈ cycloalkyl or heteroaryl bound by C₁₋₃ alkyl; and R¹³ represents H or OH or together with R¹² via the same C atom (spiro compound) or an adjacent C atom forms a five-membered or six-membered ring which may contain heteroatoms, be saturated or unsaturated, substituted or unsubstituted or be part of a polycyclic system; R¹⁴ represents respectively saturated or unsaturated, branched or unbranched, singly or multiply substituted or unsubstituted C₁₋₃ alkyl; or an acid, base, or a physiologically acceptable salt thereof.
 28. A cyclohexyl-1,4-diamine compound corresponding to formula I,

wherein n represents 1, 2, 3, 4 or 5 R¹ and R² independently of one another represent H; saturated or unsaturated, branched or unbranched, singly or multiply substituted or unsubstituted C₁₋₅ alkyl; singly or multiply substituted or unsubstituted C₃₋₈ cycloalkyl; or singly or multiply substituted or unsubstituted aryl, C₃₋₈ cycloalkyl or heteroaryl bound by C₁₋₃ alkyl; or R¹ and R² together form a ring and represent CH₂CH₂OCH₂CH₂, CH₂CH₂NR¹⁰CH₂CH₂ or (CH2)_(3-6,) wherein R¹⁰ represents H; saturated or unsaturated, branched or unbranched, singly or multiply substituted or unsubstituted C₁₋₅ alkyl singly or multiply substituted or unsubstituted C₃₋₈ cycloalkyl; singly or multiply substituted or unsubstituted aryl or heteroaryl; or singly or multiply substituted or unsubstituted aryl, C₃₋₈ cycloalkyl or heteroaryl bound by C₁₋₃ alkyl; substituted or unsubstituted C(O)phenyl, C(O)heteroaryl, C(O)C₁₋₅ alkyl; R³ represents saturated or unsaturated, branched or unbranched, singly or multiply substituted or unsubstituted C₁₋₅ alkyl; singly or multiply substituted or unsubstituted C₃₋₈ cycloalkyl; unsubstituted or singly or multiply substituted aryl or heteroaryl; unsubstituted or singly or multiply substituted aryl, heteroaryl or C₃₋₈ cycloalkyl bound by a C₁₋₃ alkyl group; R⁴ represents —(CR⁶R⁷)_(p)R⁸, wherein p represents 0, 1, 2, 3 or 4; R⁶ represents H or saturated or unsaturated, branched or unbranched, unsubstituted or singly or multiply substituted C₁₋₅ alkyl; R⁷ represents H, saturated or unsaturated, branched or unbranched, unsubstituted or singly or multiply substituted C₁₋₅ alkyl or COOR⁹; or R⁶ and R⁷ together form a ring and represent (CH₂)_(k)CHR⁸(CH₂)_(m), where k=1, 2, or 3 and m=1 or 2; R⁸ represents respectively saturated or unsaturated, branched or unbranched, unsubstituted or singly or multiply substituted C₁₋₆ alkyl; unsubstituted or singly or multiply substituted C₃₋₈ cycloalkyl, aryl or heteroaryl; R⁹ represents H or C₁₋₅ alkyl; R⁵ represents H or —(CH₂)_(l)R⁸, wherein l represents 1, 2 or 3 or R⁵ and R⁴ together form a ring and represent CH₂CHR¹⁴OCHR¹⁴CH₂, CH₂CH₂SCH₂CH₂, CH₂CH₂NR¹¹CH₂CH₂, (CR,¹²R¹³)₃₋₆ or

wherein R¹¹ represents H; saturated or unsaturated, branched or unbranched, singly or multiply substituted or unsubstituted C₁₋₅ alkyl; saturated or unsaturated, singly or multiply substituted or unsubstituted C₃₋₈ cycloalkyl; singly or multiply substituted or unsubstituted aryl or heteroaryl; or singly or multiply substituted or unsubstituted aryl, C₃₋₈ cycloalkyl or heteroaryl bound by C₁₋₃ alkyl; R¹² represents H; saturated or unsaturated, branched or unbranched, singly or multiply substituted or unsubstituted C₁₋₅ alkyl; OH; unsubstituted or singly or multiply substituted C(O)phenyl; singly or multiply substituted or unsubstituted C₃₋₈ cycloalkyl; respectively singly or multiply substituted or unsubstituted aryl or heteroaryl; or singly or multiply substituted or unsubstituted aryl, C₃₋₈ cycloalkyl or heteroaryl bound by C₁₋₃ alkyl; R¹³ represents H or OH or together with R¹² via the same C atom or an adjacent C atom forms a five-membered or six-membered ring which may contain heteroatoms, be saturated or unsaturated, substituted or unsubstituted or be part of a polycyclic system; and R¹⁴ represents respectively saturated or unsaturated, branched or unbranched, singly or multiply substituted or unsubstituted C₁₋₃ alkyl; or an acid, base, or a physiologically acceptable salt thereof. 